<PAGE>   1
      As filed with the Securities and Exchange Commission on May 13, 1999
                                            Registration No. 333-_______________

================================================================================

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                                    FORM S-8
                             REGISTRATION STATEMENT
                                      Under
                           The Securities Act of 1933

                                 COMBICHEM, INC.
             (Exact name of registrant as specified in its charter)

            DELAWARE                                      33-0617379
  (State or other jurisdiction                 (IRS Employer Identification No.)
of incorporation or organization)

                9050 CAMINO SANTA FE, SAN DIEGO, CALIFORNIA 92121
               (Address of principal executive offices) (Zip Code)


                                 COMBICHEM, INC.

                            1997 STOCK INCENTIVE PLAN
                              ---------------------
                            (Full title of the Plan)

                             DR. VINCENT ANIDO, JR.
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                                 COMBICHEM, INC.
                9050 CAMINO SANTA FE, SAN DIEGO, CALIFORNIA 92121
                     (Name and address of agent for service)
                                 (619) 530-0484
          (Telephone number, including area code, of agent for service)

                         CALCULATION OF REGISTRATION FEE

<TABLE>
<CAPTION>
=========================================================================================================================
                                                                   Proposed              Proposed
              Title of                                             Maximum               Maximum
             Securities                       Amount               Offering             Aggregate             Amount of
                to be                         to be                 Price                Offering           Registration
             Registered                   Registered(1)           per Share               Price                  Fee
             ----------                   -------------           ---------             ---------           ------------
<S>                                      <C>                      <C>                   <C>                 <C>    
1997 Stock Incentive Plan
Common Stock, par value $0.001           1,000,000 shares          $3.31(2)             $3,310,000             $920.18
per share
=========================================================================================================================
</TABLE>

(1)      This Registration Statement shall also cover any additional shares of
         Registrant's Common Stock which become issuable under the 1997 Stock
         Incentive Plan by reason of any stock dividend, stock split,
         recapitalization or other similar transaction effected without the
         Registrant's receipt of consideration which results in an increase in
         the number of the Registrant's outstanding shares of Common Stock.

(2)      Calculated solely for purposes of this offering under Rule 457(h) of
         the Securities Act of 1933, as amended, on the basis of the average of
         the high and low selling prices per share of Common Stock of CombiChem,
         Inc. on May 6, 1999, as reported by the Nasdaq national Market.


<PAGE>   2
                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

Item 3.  Incorporation of Documents by Reference

                  CombiChem, Inc. (the "Registrant") hereby incorporates by
reference into this Registration Statement the following documents previously
filed with the Securities and Exchange Commission (the "Commission"):

         (a)      The Registrant's Annual Report on Form 10-K for the fiscal
                  year ended December 31, 1998 filed with the Commission on
                  March 31, 1998, pursuant to Section 13 of the Securities
                  Exchange Act of 1934, as amended (the "1934 Act");

         (b)      The Registrant's Prospectus filed April 7, 1998 with the
                  Registrant's Registration Statement No. 333-37981 on Form S-1,
                  as amended, under the Securities Act of 1933, as amended (the
                  "1933 Act"), in which there is set forth audited financial
                  statements for the Registrant's fiscal year ended December 31,
                  1997;

         (c)      The Registrant's Registration Statement on Form 8-A filed with
                  the SEC on May 4, 1998 pursuant to Section 12 of the 1934 Act,
                  in which there is described the terms, rights and provisions
                  applicable to the Registrant's outstanding Common Stock.

                  All reports and definitive proxy or information statements
filed pursuant to Section 13(a), 13(c), 14 or 15(d) of the 1934 Act after the
date of this Registration Statement and prior to the filing of a post-effective
amendment which indicates that all securities offered hereby have been sold or
which de-registers all securities then remaining unsold shall be deemed to be
incorporated by reference into this Registration Statement and to be a part
hereof from the date of filing of such documents. Any statement contained in a
document incorporated or deemed to be incorporated by reference herein shall be
deemed to be modified or superseded for purposes of this Registration Statement
to the extent that a statement contained herein or in any subsequently filed
document which also is deemed to be incorporated by reference herein modifies or
supersedes such statement. Any such statement so modified or superseded shall
not be deemed, except as so modified or superseded, to constitute a part of this
Registration Statement.

Item 4.  Description of Securities

                  Not Applicable.

Item 5.  Interests of Named Experts and Counsel

     Faye H. Russell, a partner in the law firm of Brobeck, Phleger & Harrison,
LLP, which provides legal services to the Registrant as regular outside counsel,
serves as Secretary of Registrant.

Item 6.  Indemnification of Directors and Officers

         Section 145 of the Delaware General Corporation Law permits
indemnification of officers and directors of the Company under certain
conditions and subject to certain limitations. Section 145 of the Delaware
General Corporation Law also provides that a corporation has the power to
purchase and maintain insurance on behalf of its officers and directors against
any liability asserted against such person and incurred by him or her in such
capacity, or arising out of his or her status as such, whether or not the
corporation would have the power to indemnify him or her against such liability
under the provisions of Section 145 of the Delaware General Corporation Law.

         Article VII, Section 1 of the Restated Bylaws of the Registrant
provides that the Registrant shall indemnify its directors and executive
officers to the fullest extent not prohibited by the Delaware General
Corporation Law. The rights to indemnify thereunder continue as to a person who
has ceased to be a director, officer, employee or agent and inure to the benefit
of the heirs, executors and administrators of the person. In addition, expenses
incurred by a director or executive officer in defending any civil, criminal,
administrative or investigative action, suit or proceeding by reason of the fact
that he or she is or was a director or officer of the Registrant (or was serving
at the


                                      II-1
<PAGE>   3
Registrant's request as a director or officer of another corporation) shall be
paid by the Registrant in advance of the final disposition of such action, suit
or proceeding upon receipt of an undertaking by or on behalf of such director or
officer to repay such amount if it shall ultimately be determined that he or she
is not entitled to be indemnified by the Registrant as authorized by the
relevant section of the Delaware General Corporation Law.

         As permitted by Section 102(b)(7) of the Delaware General Corporation
Law, Article V, Section (A) of the Registrant's Restated Certificate of
Incorporation provides that a director of the Registrant shall not be personally
liable for monetary damages for breach of fiduciary duty as a director, except
for liability (i) for any breach of the director's duty of loyalty to the
Registrant or its stockholders, (ii) for acts or omissions not in good faith or
acts or omissions that involve intentional misconduct or a knowing violation of
law, (iii) under Section 174 of the Delaware General Corporation Law or (iv) for
any transaction from which the director derived any improper personal benefit.

         The Registrant has entered into indemnification agreements with each of
its directors and executive officers. Generally, the indemnification agreements
attempt to provide the maximum protection permitted by Delaware law as it may be
amended from time to time. Moreover, the indemnification agreements provide for
certain additional indemnification. Under such additional indemnification
provisions, however, an individual will not receive indemnification for
judgments, settlements or expenses if he or she is found liable to the
Registrant (except to the extent the court determines he or she is fairly and
reasonably entitled to indemnity for expenses), for settlements not approved by
the Registrant or for settlements and expenses if the settlement is not approved
by the court. The indemnification agreements provide for the Registrant to
advance to the individual any and all reasonable expenses (including legal fees
and expenses) incurred in investigating or defending any such action, suit or
proceeding. In order or receive an advance of expenses, the individual must
submit to the Registrant copies of invoices presented to him or her for such
expenses. Also, the individual must repay such advances upon a final judicial
decision that he or she is not entitled to indemnification. The Registrant has
purchased directors' and officers' liability insurance. The Registrant intends
to enter into additional indemnification agreements with each of its directors
and executive officers to effectuate these indemnity provisions.

Item 7.  Exemption from Registration Claimed

                  Not Applicable.

Item 8.  Exhibits

<TABLE>
<CAPTION>
Exhibit Number    Exhibit
--------------    -------
<S>               <C>
   4.1            Instruments   Defining  the  Rights  of   Stockholders.   Reference  is  made  to   Registrant's
                  Registration  Statement on Form 8-A,  together with the amendments and exhibits  thereto,  which
                  are incorporated herein by reference pursuant to Item 3(c).
   5.1            Opinion and consent of Brobeck, Phleger & Harrison LLP.
   23.1           Consent of Ernst & Young LLP, Independent Accountants.
   23.2           Consent of Brobeck, Phleger & Harrison LLP is contained in Exhibit 5.1.
   24.1           Power of Attorney.  Reference is made to page II-4 of this Registration Statement.
   99.1           CombiChem, Inc. 1997 Stock Incentive Plan.
   99.2+          Form of Notice of Grant of Stock Option (Exhibit 10.48).
   99.3+          Form of Stock Option Agreement (Exhibit 10.49).
   99.4+          Form of Addendum to Stock Option Agreement (Involuntary Termination Following Corporate
                  Transaction/Change in Control) (Exhibit 10.50).
   99.5+          Form of Addendum to Stock Option Agreement (Limited Stock Appreciation Right) (Exhibit 10.51)
   99.6+          Form of Stock Issuance Agreement (Exhibit 10.52).
   99.7+          Form of Addendum to Stock Issuance Agreement (Involuntary Termination Following Corporate
                  Transaction/Change in Control) (Exhibit 10.53).
   99.8+          Form of Notice of Grant of Automatic Stock Option (Initial Grant) (Exhibit 10.54).
   99.9+          Form of Notice of Grant of Automatic Stock Option (Annual Grant) (Exhibit 10.55).
   99.10+         Form of Automatic Stock Option Agreement (Exhibit 10.56).
   99.11+         Form of Stock Purchase Agreement(Exhibit 10.57).
</TABLE>

-----------------


                                      II-2
<PAGE>   4
+These exhibits were previously filed as part of, and are hereby incorporated by
reference to, the same numbered exhibit (except as otherwise noted) filed with
the Registrant's Amendment No. 2 to Registration Statement on Form S-1
(Commission No. 333-37981) initially filed on December 3, 1997, as amended.


Item 9.  Undertakings

                  A.       The undersigned Registrant hereby undertakes: (1) to
file, during any period in which offers or sales are being made, a
post-effective amendment to this Registration Statement: (i) to include any
prospectus required by Section 10(a)(3) of the 1933 Act, (ii) to reflect in the
prospectus any facts or events arising after the effective date of this
Registration Statement (or the most recent post-effective amendment thereof)
which, individually or in the aggregate, represent a fundamental change in the
information set forth in this Registration Statement and (iii) to include any
material information with respect to the plan of distribution not previously
disclosed in this Registration Statement or any material change to such
information in this Registration Statement; provided, however, that clauses
(1)(i) and (1)(ii) shall not apply if the information required to be included in
a post-effective amendment by those clauses is contained in periodic reports
filed by the Registrant pursuant to Section 13 or Section 15(d) of the 1934 Act
that are incorporated by reference into this Registration Statement; (2) that
for the purpose of determining any liability under the 1933 Act each such
post-effective amendment shall be deemed to be a new registration statement
relating to the securities offered therein and the offering of such securities
at that time shall be deemed to be the initial bona fide offering thereof; and
(3) to remove from registration by means of a post-effective amendment any of
the securities being registered which remain unsold at the termination of the
1996 Stock Incentive Plan.

                  B.       The undersigned Registrant hereby undertakes that,
for purposes of determining any liability under the 1933 Act, each filing of the
Registrant's annual report pursuant to Section 13(a) or Section 15(d) of the
1934 Act that is incorporated by reference into this Registration Statement
shall be deemed to be a new registration statement relating to the securities
offered therein, and the offering of such securities at that time shall be
deemed to be the initial bona fide offering thereof.

                  C.       Insofar as indemnification for liabilities arising
under the 1933 Act may be permitted to directors, officers or controlling
persons of the Registrant pursuant to the indemnification provisions summarized
in Item 6 or otherwise, the Registrant has been advised that, in the opinion of
the Commission, such indemnification is against public policy as expressed in
the 1933 Act and is, therefore, unenforceable. In the event that a claim for
indemnification against such liabilities (other than the payment by the
Registrant of expenses incurred or paid by a director, officer, or controlling
person of the Registrant in the successful defense of any action, suit or
proceeding) is asserted by such director, officer or controlling person in
connection with the securities being registered, the Registrant will, unless in
the opinion of its counsel the matter has been settled by controlling precedent,
submit to a court of appropriate jurisdiction the question whether such
indemnification by it is against public policy as expressed in the 1933 Act and
will be governed by the final adjudication of such issue.


                                      II-3
<PAGE>   5
                                   SIGNATURES

                  Pursuant to the requirements of the Securities Act of 1933, as
amended, the Registrant certifies that it has reasonable grounds to believe that
it meets all of the requirements for filing on Form S-8, and has duly caused
this Registration Statement to be signed on its behalf by the undersigned,
thereunto duly authorized, in the City of San Diego, State of California on this
13th day of May, 1999.

                                 COMBICHEM, INC.


                                 By:  /s/ Vicente Anido, Jr., Ph.D.
                                      ------------------------------------------
                                      Vicente Anido, Jr., Ph.D.
                                      President and Chief Executive Officer


                                POWER OF ATTORNEY

                  KNOW ALL PERSONS BY THESE PRESENTS, that each person whose
signature appears below constitutes and appoints Vicente Anido and Peter L.
Myers, and each of them, as such person's true and lawful attorneys-in-fact and
agents, with full power of substitution and resubstitution, for such person and
in such person's name, place and stead, in any and all capacities, to sign any
and all amendments (including post-effective amendments) to this Registration
Statement, and to file same, with all exhibits thereto, and other documents in
connection therewith, with the Securities and Exchange Commission, granting unto
said attorneys-in-fact and agents, and each of them, full power and authority to
do and perform each and every act and thing requisite and necessary to be done
in connection therewith, as fully to all intents and purposes as such person
might or could do in person, hereby ratifying and confirming all that said
attorneys-in-fact and agents, or any of them, or their or his or her
substitutes, may lawfully do or cause to be done by virtue thereof.

                  Pursuant to the requirements of the Securities Act of 1933, as
amended, this Registration Statement has been signed below by the following
persons on behalf of the Registrant and in the capacities and on the dates
indicated:

<TABLE>
<CAPTION>
Signature                                 Title                                            Date
---------                                 -----                                            ----
<S>                                       <C>                                              <C> 
     /s/ Vicente Anido, Jr.               President, Chief Executive                       May 13, 1999
----------------------------------        Office and Director                
Vicente Anido, Jr., Ph.D.                 (Principal Executive Officer and   
                                          Principal Financial and Accounting 
                                          Officer)                           
                                          

     /s/ Peter L. Myers                   Vice President, Chief Scientific Officer,        May 13, 1999
----------------------------------        Chief Operating Officer and Director
Peter L. Myers, Ph.D.                     

                                          Director                                         May 13, 1999
----------------------------------
Philippe O. Chambon, M.D., Ph.D.

     /s/ M. J. Pazzani                    Director                                         May 13, 1999
----------------------------------
Michael J. Pazzani, Ph.D.

     /s/ Arthur Reidel                    Director                                         May 13, 1999
----------------------------------
Arthur Reidel

     /s/ W.A. Scott                       Director                                         May 13, 1999
----------------------------------
William Scott, Ph.D.
</TABLE>


                                      II-4
<PAGE>   6





                       SECURITIES AND EXCHANGE COMMISSION

                             WASHINGTON, D.C. 20549


                                    EXHIBITS

                                       TO

                                    FORM S-8

                                      UNDER

                             SECURITIES ACT OF 1933


                                 COMBICHEM, INC.


<PAGE>   7
                                  EXHIBIT INDEX

<TABLE>
<CAPTION>
Exhibit Number    Exhibit
--------------    -------
<S>               <C>
   4.1            Instruments   Defining  the  Rights  of   Stockholders.   Reference  is  made  to   Registrant's
                  Registration  Statement on Form 8-A,  together with the amendments and exhibits  thereto,  which
                  are incorporated herein by reference pursuant to Item 3(c).
   5.1            Opinion and consent of Brobeck, Phleger & Harrison LLP.
   23.1           Consent of Ernst & Young LLP, Independent Auditors.
   23.2           Consent of Brobeck, Phleger & Harrison LLP is contained in Exhibit 5.
   24.1           Power of Attorney.  Reference is made to page II-4 of this Registration Statement.
   99.1           CombiChem, Inc. 1997 Stock Incentive Plan.
   99.2+          Form of Notice of Grant of Stock Option (Exhibit 10.48).
   99.3+          Form of Stock Option Agreement (Exhibit 10.49).
   99.4+          Form of Addendum to Stock Option Agreement (Involuntary Termination Following Corporate
                  Transaction/Change in Control) (Exhibit 10.50).
   99.5+          Form of Addendum to Stock Option Agreement (Limited Stock Appreciation Right) (Exhibit 10.51)
   99.6+          Form of Stock Issuance Agreement (Exhibit 10.52).
   99.7+          Form of Addendum to Stock Issuance Agreement (Involuntary Termination Following Corporate
                  Transaction/Change in Control) (Exhibit 10.53).
   99.8+          Form of Notice of Grant of Automatic Stock Option (Initial Grant) (Exhibit 10.54).
   99.9+          Form of Notice of Grant of Automatic Stock Option (Annual Grant) (Exhibit 10.55).
   99.10+         Form of Automatic Stock Option Agreement (Exhibit 10.56).
   99.11+         Form of Stock Purchase Agreement(Exhibit 10.57).
</TABLE>
-----------------

+These exhibits were previously filed as part of, and are hereby incorporated by
reference to, the same numbered exhibit (except as otherwise noted) filed with
the Registrant's Amendment No. 2 to Registration Statement on Form S-1
(Commission No. 333-37981) initially filed on December 3, 1997, as amended.
[{"type": "S-8", "sequence": "1", "description": "FORM S-8", "secsgml_size_bytes": 22833}]
{"company-data": {"conformed-name": "COMBICHEM INC", "cik": "0001002276", "assigned-sic": "8731", "irs-number": "330617379", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-78361", "film-number": "99619685"}, "business-address": {"street1": "9050 CAMINO", "street2": "SUITE 200", "city": "SAN DIEGO", "state": "CA", "zip": "92121", "phone": "6195300484"}, "mail-address": {"street1": "9050 CAMINO SANTA FE", "city": "SAN DIEGO", "state": "CA", "zip": "92121"}}
1
      As filed with the Securities and Exchange Commission on May 13, 1999
                                            Registration No. 333-_______________

================================================================================

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                                    FORM S-8
                             REGISTRATION STATEMENT
                                      Under
                           The Securities Act of 1933

                                 COMBICHEM, INC.
             (Exact name of registrant as specified in its charter)

            DELAWARE                                      33-0617379
  (State or other jurisdiction                 (IRS Employer Identification No.)
of incorporation or organization)

                9050 CAMINO SANTA FE, SAN DIEGO, CALIFORNIA 92121
               (Address of principal executive offices) (Zip Code)

                                 COMBICHEM, INC.

                            1997 STOCK INCENTIVE PLAN
                              ---------------------
                            (Full title of the Plan)

                             DR. VINCENT ANIDO, JR.
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                                 COMBICHEM, INC.
                9050 CAMINO SANTA FE, SAN DIEGO, CALIFORNIA 92121
                     (Name and address of agent for service)
                                 (619) 530-0484
          (Telephone number, including area code, of agent for service)

                         CALCULATION OF REGISTRATION FEE
=========================================================================================================================
                                                                   Proposed              Proposed
              Title of                                             Maximum               Maximum
             Securities                       Amount               Offering             Aggregate             Amount of
                to be                         to be                 Price                Offering           Registration
             Registered                   Registered(1)           per Share               Price                  Fee
             ----------                   -------------           ---------             ---------           ------------
1997 Stock Incentive Plan
Common Stock, par value $0.001           1,000,000 shares          $3.31(2)             $3,310,000             $920.18
per share
=========================================================================================================================
(1)      This Registration Statement shall also cover any additional shares of
         Registrant's Common Stock which become issuable under the 1997 Stock
         Incentive Plan by reason of any stock dividend, stock split,
         recapitalization or other similar transaction effected without the
         Registrant's receipt of consideration which results in an increase in
         the number of the Registrant's outstanding shares of Common Stock.

(2)      Calculated solely for purposes of this offering under Rule 457(h) of
         the Securities Act of 1933, as amended, on the basis of the average of
         the high and low selling prices per share of Common Stock of CombiChem,
         Inc. on May 6, 1999, as reported by the Nasdaq national Market.
2
                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

Item 3.  Incorporation of Documents by Reference

                  CombiChem, Inc. (the "Registrant") hereby incorporates by
reference into this Registration Statement the following documents previously
filed with the Securities and Exchange Commission (the "Commission"):

         (a)      The Registrant's Annual Report on Form 10-K for the fiscal
                  year ended December 31, 1998 filed with the Commission on
                  March 31, 1998, pursuant to Section 13 of the Securities
                  Exchange Act of 1934, as amended (the "1934 Act");

         (b)      The Registrant's Prospectus filed April 7, 1998 with the
                  Registrant's Registration Statement No. 333-37981 on Form S-1,
                  as amended, under the Securities Act of 1933, as amended (the
                  "1933 Act"), in which there is set forth audited financial
                  statements for the Registrant's fiscal year ended December 31,
                  1997;

         (c)      The Registrant's Registration Statement on Form 8-A filed with
                  the SEC on May 4, 1998 pursuant to Section 12 of the 1934 Act,
                  in which there is described the terms, rights and provisions
                  applicable to the Registrant's outstanding Common Stock.

                  All reports and definitive proxy or information statements
filed pursuant to Section 13(a), 13(c), 14 or 15(d) of the 1934 Act after the
date of this Registration Statement and prior to the filing of a post-effective
amendment which indicates that all securities offered hereby have been sold or
which de-registers all securities then remaining unsold shall be deemed to be
incorporated by reference into this Registration Statement and to be a part
hereof from the date of filing of such documents. Any statement contained in a
document incorporated or deemed to be incorporated by reference herein shall be
deemed to be modified or superseded for purposes of this Registration Statement
to the extent that a statement contained herein or in any subsequently filed
document which also is deemed to be incorporated by reference herein modifies or
supersedes such statement. Any such statement so modified or superseded shall
not be deemed, except as so modified or superseded, to constitute a part of this
Registration Statement.

Item 4.  Description of Securities

                  Not Applicable.

Item 5.  Interests of Named Experts and Counsel

     Faye H. Russell, a partner in the law firm of Brobeck, Phleger & Harrison,
LLP, which provides legal services to the Registrant as regular outside counsel,
serves as Secretary of Registrant.

Item 6.  Indemnification of Directors and Officers

         Section 145 of the Delaware General Corporation Law permits
indemnification of officers and directors of the Company under certain
conditions and subject to certain limitations. Section 145 of the Delaware
General Corporation Law also provides that a corporation has the power to
purchase and maintain insurance on behalf of its officers and directors against
any liability asserted against such person and incurred by him or her in such
capacity, or arising out of his or her status as such, whether or not the
corporation would have the power to indemnify him or her against such liability
under the provisions of Section 145 of the Delaware General Corporation Law.

         Article VII, Section 1 of the Restated Bylaws of the Registrant
provides that the Registrant shall indemnify its directors and executive
officers to the fullest extent not prohibited by the Delaware General
Corporation Law. The rights to indemnify thereunder continue as to a person who
has ceased to be a director, officer, employee or agent and inure to the benefit
of the heirs, executors and administrators of the person. In addition, expenses
incurred by a director or executive officer in defending any civil, criminal,
administrative or investigative action, suit or proceeding by reason of the fact
that he or she is or was a director or officer of the Registrant (or was serving
at the

                                      II-1
3
Registrant's request as a director or officer of another corporation) shall be
paid by the Registrant in advance of the final disposition of such action, suit
or proceeding upon receipt of an undertaking by or on behalf of such director or
officer to repay such amount if it shall ultimately be determined that he or she
is not entitled to be indemnified by the Registrant as authorized by the
relevant section of the Delaware General Corporation Law.

         As permitted by Section 102(b)(7) of the Delaware General Corporation
Law, Article V, Section (A) of the Registrant's Restated Certificate of
Incorporation provides that a director of the Registrant shall not be personally
liable for monetary damages for breach of fiduciary duty as a director, except
for liability (i) for any breach of the director's duty of loyalty to the
Registrant or its stockholders, (ii) for acts or omissions not in good faith or
acts or omissions that involve intentional misconduct or a knowing violation of
law, (iii) under Section 174 of the Delaware General Corporation Law or (iv) for
any transaction from which the director derived any improper personal benefit.

         The Registrant has entered into indemnification agreements with each of
its directors and executive officers. Generally, the indemnification agreements
attempt to provide the maximum protection permitted by Delaware law as it may be
amended from time to time. Moreover, the indemnification agreements provide for
certain additional indemnification. Under such additional indemnification
provisions, however, an individual will not receive indemnification for
judgments, settlements or expenses if he or she is found liable to the
Registrant (except to the extent the court determines he or she is fairly and
reasonably entitled to indemnity for expenses), for settlements not approved by
the Registrant or for settlements and expenses if the settlement is not approved
by the court. The indemnification agreements provide for the Registrant to
advance to the individual any and all reasonable expenses (including legal fees
and expenses) incurred in investigating or defending any such action, suit or
proceeding. In order or receive an advance of expenses, the individual must
submit to the Registrant copies of invoices presented to him or her for such
expenses. Also, the individual must repay such advances upon a final judicial
decision that he or she is not entitled to indemnification. The Registrant has
purchased directors' and officers' liability insurance. The Registrant intends
to enter into additional indemnification agreements with each of its directors
and executive officers to effectuate these indemnity provisions.

Item 7.  Exemption from Registration Claimed

                  Not Applicable.

Item 8.  Exhibits
Exhibit Number    Exhibit
--------------    -------
4.1            Instruments   Defining  the  Rights  of   Stockholders.   Reference  is  made  to   Registrant's
                  Registration  Statement on Form 8-A,  together with the amendments and exhibits  thereto,  which
                  are incorporated herein by reference pursuant to Item 3(c).
   5.1            Opinion and consent of Brobeck, Phleger & Harrison LLP.
   23.1           Consent of Ernst & Young LLP, Independent Accountants.
   23.2           Consent of Brobeck, Phleger & Harrison LLP is contained in Exhibit 5.1.
   24.1           Power of Attorney.  Reference is made to page II-4 of this Registration Statement.
   99.1           CombiChem, Inc. 1997 Stock Incentive Plan.
   99.2+          Form of Notice of Grant of Stock Option (Exhibit 10.48).
   99.3+          Form of Stock Option Agreement (Exhibit 10.49).
   99.4+          Form of Addendum to Stock Option Agreement (Involuntary Termination Following Corporate
                  Transaction/Change in Control) (Exhibit 10.50).
   99.5+          Form of Addendum to Stock Option Agreement (Limited Stock Appreciation Right) (Exhibit 10.51)
   99.6+          Form of Stock Issuance Agreement (Exhibit 10.52).
   99.7+          Form of Addendum to Stock Issuance Agreement (Involuntary Termination Following Corporate
                  Transaction/Change in Control) (Exhibit 10.53).
   99.8+          Form of Notice of Grant of Automatic Stock Option (Initial Grant) (Exhibit 10.54).
   99.9+          Form of Notice of Grant of Automatic Stock Option (Annual Grant) (Exhibit 10.55).
   99.10+         Form of Automatic Stock Option Agreement (Exhibit 10.56).
   99.11+         Form of Stock Purchase Agreement(Exhibit 10.57).
-----------------

                                      II-2
4
+These exhibits were previously filed as part of, and are hereby incorporated by
reference to, the same numbered exhibit (except as otherwise noted) filed with
the Registrant's Amendment No. 2 to Registration Statement on Form S-1
(Commission No. 333-37981) initially filed on December 3, 1997, as amended.

Item 9.  Undertakings

                  A.       The undersigned Registrant hereby undertakes: (1) to
file, during any period in which offers or sales are being made, a
post-effective amendment to this Registration Statement: (i) to include any
prospectus required by Section 10(a)(3) of the 1933 Act, (ii) to reflect in the
prospectus any facts or events arising after the effective date of this
Registration Statement (or the most recent post-effective amendment thereof)
which, individually or in the aggregate, represent a fundamental change in the
information set forth in this Registration Statement and (iii) to include any
material information with respect to the plan of distribution not previously
disclosed in this Registration Statement or any material change to such
information in this Registration Statement; provided, however, that clauses
(1)(i) and (1)(ii) shall not apply if the information required to be included in
a post-effective amendment by those clauses is contained in periodic reports
filed by the Registrant pursuant to Section 13 or Section 15(d) of the 1934 Act
that are incorporated by reference into this Registration Statement; (2) that
for the purpose of determining any liability under the 1933 Act each such
post-effective amendment shall be deemed to be a new registration statement
relating to the securities offered therein and the offering of such securities
at that time shall be deemed to be the initial bona fide offering thereof; and
(3) to remove from registration by means of a post-effective amendment any of
the securities being registered which remain unsold at the termination of the
1996 Stock Incentive Plan.

                  B.       The undersigned Registrant hereby undertakes that,
for purposes of determining any liability under the 1933 Act, each filing of the
Registrant's annual report pursuant to Section 13(a) or Section 15(d) of the
1934 Act that is incorporated by reference into this Registration Statement
shall be deemed to be a new registration statement relating to the securities
offered therein, and the offering of such securities at that time shall be
deemed to be the initial bona fide offering thereof.

                  C.       Insofar as indemnification for liabilities arising
under the 1933 Act may be permitted to directors, officers or controlling
persons of the Registrant pursuant to the indemnification provisions summarized
in Item 6 or otherwise, the Registrant has been advised that, in the opinion of
the Commission, such indemnification is against public policy as expressed in
the 1933 Act and is, therefore, unenforceable. In the event that a claim for
indemnification against such liabilities (other than the payment by the
Registrant of expenses incurred or paid by a director, officer, or controlling
person of the Registrant in the successful defense of any action, suit or
proceeding) is asserted by such director, officer or controlling person in
connection with the securities being registered, the Registrant will, unless in
the opinion of its counsel the matter has been settled by controlling precedent,
submit to a court of appropriate jurisdiction the question whether such
indemnification by it is against public policy as expressed in the 1933 Act and
will be governed by the final adjudication of such issue.

                                      II-3
5
                                   SIGNATURES

                  Pursuant to the requirements of the Securities Act of 1933, as
amended, the Registrant certifies that it has reasonable grounds to believe that
it meets all of the requirements for filing on Form S-8, and has duly caused
this Registration Statement to be signed on its behalf by the undersigned,
thereunto duly authorized, in the City of San Diego, State of California on this
13th day of May, 1999.

                                 COMBICHEM, INC.

                                 By:  /s/ Vicente Anido, Jr., Ph.D.
                                      ------------------------------------------
                                      Vicente Anido, Jr., Ph.D.
                                      President and Chief Executive Officer

                                POWER OF ATTORNEY

                  KNOW ALL PERSONS BY THESE PRESENTS, that each person whose
signature appears below constitutes and appoints Vicente Anido and Peter L.
Myers, and each of them, as such person's true and lawful attorneys-in-fact and
agents, with full power of substitution and resubstitution, for such person and
in such person's name, place and stead, in any and all capacities, to sign any
and all amendments (including post-effective amendments) to this Registration
Statement, and to file same, with all exhibits thereto, and other documents in
connection therewith, with the Securities and Exchange Commission, granting unto
said attorneys-in-fact and agents, and each of them, full power and authority to
do and perform each and every act and thing requisite and necessary to be done
in connection therewith, as fully to all intents and purposes as such person
might or could do in person, hereby ratifying and confirming all that said
attorneys-in-fact and agents, or any of them, or their or his or her
substitutes, may lawfully do or cause to be done by virtue thereof.

                  Pursuant to the requirements of the Securities Act of 1933, as
amended, this Registration Statement has been signed below by the following
persons on behalf of the Registrant and in the capacities and on the dates
indicated:
Signature                                 Title                                            Date
---------                                 -----                                            ----
/s/ Vicente Anido, Jr.               President, Chief Executive                       May 13, 1999
----------------------------------        Office and Director                
Vicente Anido, Jr., Ph.D.                 (Principal Executive Officer and   
                                          Principal Financial and Accounting 
                                          Officer)                           
                                          

     /s/ Peter L. Myers                   Vice President, Chief Scientific Officer,        May 13, 1999
----------------------------------        Chief Operating Officer and Director
Peter L. Myers, Ph.D.                     

                                          Director                                         May 13, 1999
----------------------------------
Philippe O. Chambon, M.D., Ph.D.

     /s/ M. J. Pazzani                    Director                                         May 13, 1999
----------------------------------
Michael J. Pazzani, Ph.D.

     /s/ Arthur Reidel                    Director                                         May 13, 1999
----------------------------------
Arthur Reidel

     /s/ W.A. Scott                       Director                                         May 13, 1999
----------------------------------
William Scott, Ph.D.
II-4
6

                       SECURITIES AND EXCHANGE COMMISSION

                             WASHINGTON, D.C. 20549

                                    EXHIBITS

                                       TO

                                    FORM S-8

                                      UNDER

                             SECURITIES ACT OF 1933

                                 COMBICHEM, INC.
7
                                  EXHIBIT INDEX
Exhibit Number    Exhibit
--------------    -------
4.1            Instruments   Defining  the  Rights  of   Stockholders.   Reference  is  made  to   Registrant's
                  Registration  Statement on Form 8-A,  together with the amendments and exhibits  thereto,  which
                  are incorporated herein by reference pursuant to Item 3(c).
   5.1            Opinion and consent of Brobeck, Phleger & Harrison LLP.
   23.1           Consent of Ernst & Young LLP, Independent Auditors.
   23.2           Consent of Brobeck, Phleger & Harrison LLP is contained in Exhibit 5.
   24.1           Power of Attorney.  Reference is made to page II-4 of this Registration Statement.
   99.1           CombiChem, Inc. 1997 Stock Incentive Plan.
   99.2+          Form of Notice of Grant of Stock Option (Exhibit 10.48).
   99.3+          Form of Stock Option Agreement (Exhibit 10.49).
   99.4+          Form of Addendum to Stock Option Agreement (Involuntary Termination Following Corporate
                  Transaction/Change in Control) (Exhibit 10.50).
   99.5+          Form of Addendum to Stock Option Agreement (Limited Stock Appreciation Right) (Exhibit 10.51)
   99.6+          Form of Stock Issuance Agreement (Exhibit 10.52).
   99.7+          Form of Addendum to Stock Issuance Agreement (Involuntary Termination Following Corporate
                  Transaction/Change in Control) (Exhibit 10.53).
   99.8+          Form of Notice of Grant of Automatic Stock Option (Initial Grant) (Exhibit 10.54).
   99.9+          Form of Notice of Grant of Automatic Stock Option (Annual Grant) (Exhibit 10.55).
   99.10+         Form of Automatic Stock Option Agreement (Exhibit 10.56).
   99.11+         Form of Stock Purchase Agreement(Exhibit 10.57).
-----------------

+These exhibits were previously filed as part of, and are hereby incorporated by
reference to, the same numbered exhibit (except as otherwise noted) filed with
the Registrant's Amendment No. 2 to Registration Statement on Form S-1
(Commission No. 333-37981) initially filed on December 3, 1997, as amended.