<PAGE>

     As filed with the Securities and Exchange Commission on January 3, 2001
                                                          REGISTRATION NO. 333 -
================================================================================

                      SECURITIES AND EXCHANGE COMMISSION
                            WASHINGTON, D.C. 20549

                                   FORM S-8
                            REGISTRATION STATEMENT
                                   under the
                            SECURITIES ACT OF 1933

                           ORCHID BIOSCIENCES, INC.
            (Exact name of Registrant as specified in its charter)

             Delaware                                    22-3392819
    (State or other jurisdiction                      (I.R.S. Employer
  of incorporation or organization)                 Identification No.)

                             303 College Road East
                              Princeton, NJ 08540
                                (609) 750-2200
                   (Address of Principal Executive Offices)

                           ORCHID BIOSCIENCES, INC.
                           1995 STOCK INCENTIVE PLAN

                           ORCHID BIOSCIENCES, INC.
                          2000 EMPLOYEE, DIRECTOR AND
                             CONSULTANT STOCK PLAN
                           (Full title of the plan)

                             Dale R. Pfost, Ph.D.
                           ORCHID BIOSCIENCES, INC.
                             303 College Road East
                              Princeton, NJ 08540
                                (609) 750-2200
(Name, address, including zip code, and telephone number, including area code,
                             of agent for service)

<TABLE>
<CAPTION>
                                             CALCULATION OF REGISTRATION FEE
===========================================================================================================================
 Title of securities       Amount to be        Proposed Maximum offering     Proposed Maximum aggregate       Amount of
  to be registered        registered/(1)/         price per share/(2)/           offering price/(2)/       registration fee
---------------------------------------------------------------------------------------------------------------------------
<S>                       <C>                  <C>                           <C>                           <C>
Common Stock, par value     3,581,351                   $6.218                     $22,268,841                $5,567.21
$0.001 per share            1,418,649                   $8.000                     $11,349,192                $2,837.30
                            ---------                                                                        ----------
                            5,000,000                                                                         $8,404.51
===========================================================================================================================
</TABLE>

(1) The number of shares of common stock, par value $0.001 per share (the
    "Common Stock"), stated above consists of the aggregate number of shares
    which may be sold upon the exercise of options (i) which have been granted
    and which are currently outstanding and (ii) which may hereafter be granted,
    under the Orchid BioSciences, Inc. 1995 Stock Incentive Plan and the Orchid
    BioSciences, Inc. 2000 Employee, Director and Consultant Stock Plan (the
    "Plans") and which have not been previously registered under the Securities
    Act of 1933, as amended (the "Securities Act").  The maximum number of
    shares which may be sold upon the exercise of such options granted under the
    Plans is subject to adjustment in accordance with certain anti-dilution and
    other provisions of the Plans.  Accordingly, pursuant to Rule 416 under the
    Securities Act, this Registration Statement covers, in addition to the
    number of shares stated above, an indeterminate number of shares which may
    be subject to grant or otherwise issuable after the operation of any such
    anti-dilution and other provisions.

(2) This calculation is made solely for the purpose of determining the
    registration fee pursuant to the provisions of Rule 457(h) under the
    Securities Act as follows: (i) in the case of shares of Common Stock which
    may be purchased upon exercise of outstanding options, the fee is calculated
    on the basis of the price at which options may be exercised; and (ii) in the
    case of shares of Common Stock for which options have not yet been granted
    and the option price of which is therefore unknown, the fee is calculated on
    the basis of the average of the high and low sale prices per share of Common
    Stock on the Nasdaq National Market as of a date (December 22, 2000) within
    5 business days prior to filing this Registration Statement.

________________________________________________________________________________
<PAGE>

                               EXPLANATORY NOTE
                               ----------------

     In accordance with the instructional Note to Part I of Form S-8 as
promulgated by the Securities and Exchange Commission, the information specified
by Part I of Form S-8 has been omitted from this Registration Statement on Form
S-8 for offers of shares of Common Stock pursuant to the Plans.
<PAGE>

                                    PART II

              INFORMATION REQUIRED IN THE REGISTRATION STATEMENT


Item 3.  Incorporation of Certain Documents by Reference.
--------------------------------------------------------

     The following documents filed by the Registrant with the Commission are
incorporated herein by reference:

     (a) Our prospectus filed pursuant to Rule 424(b) under the Securities Act
  of 1933, as amended, containing our audited financial statements for the
  fiscal year ended December 31, 1999, filed on May 4, 2000;

     (b) Our report on Form 10-Q/A for the quarterly period ended March 31,
  2000, filed on August 10, 2000, our report on Form 10-Q for the quarterly
  period ended June 30, 2000, filed on August 15, 2000, and our report on Form
  10-Q for the quarterly period ended September 30, 2000 filed on November 14,
  2000; and

     (c) The description of the Common Stock contained in the our Registration
  Statement on Form 8-A filed under the Securities Exchange Act of 1934,
  including any amendment or report filed for the purpose of updating such
  description.

     All reports and other documents filed by the Registrant after the date
hereof pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Securities
Exchange Act of 1934 prior to the filing of a post-effective amendment which
indicates that all securities offered hereby have been sold or which deregisters
all securities then remaining unsold, shall be deemed to be incorporated by
reference herein and to be part hereof from the date of filing of such reports
and documents.

Item 4.  Description of Securities.
----------------------------------

     Not applicable.

Item 5.  Interests of Named Experts and Counsel.
-----------------------------------------------

     This Registration Statement was prepared for us by Mintz, Levin, Cohn,
Ferris, Glovsky and Popeo, P.C., Boston, Massachusetts. Attorneys at Mintz Levin
own an aggregate of 604 shares of Common Stock.
<PAGE>

     Item 6.  Indemnification of Directors and Officers.
     --------------------------------------------------

     Incorporated herein by reference from Registration Statement on Form S-1,
No. 333-30774.

Item 7.  Exemption from Registration Claimed.
--------------------------------------------

     Not applicable.

Item 8.  Exhibits.
-----------------

 Exhibit
 -------
  Number                       Description of Exhibits
  ------        -------------------------------------------------------

4.1       --Restated Certificate of Incorporation of the Company (incorporated
          by reference to Exhibit 3.2 to the Registrant's Registration Statement
          on Form S-1, as amended, No, 333-30774, effective May 4, 2000).

4.2       --Bylaws of the Company (incorporated by reference to Exhibit 3.3 to
          the Registrant's Registration Statement on Form S-1, as amended, No,
          333-30774, effective May 4, 2000).

4.3       --Specimen Certificate for Shares of Common Stock (incorporated by
          reference to Exhibit 4.1 to the Registrant's Registration Statement on
          Form S-1, as amended, No, 333-30773, effective May 4, 2000).

5.1       --Opinion of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
          regarding the legality of the common stock being registered.

23.1      --Consent of KPMG LLP (filed herewith).

23.2      --Consent of KPMG LLP (filed herewith).

23.3      --Consent of Deloitte & Touche LLP (filed herewith).

23.4      --Consent of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
          (included in opinion of counsel filed as Exhibit 5.1).

24.1      --Powers of Attorney (included in Signature Page).

99.1      --Orchid BioSciences, Inc. 1995 Stock Incentive Plan (Filed as Exhibit
          10.1 to the Registration Statement on Form S-1, as amended, No. 333-
          30774, and incorporated herein by reference).

                                     II-2
<PAGE>

99.2      --Orchid BioSciences, Inc. 2000 Employee, Director and Consultant
          Stock Plan (Filed as Exhibit 10.2 to the Registration Statement on
          Form S-1, as amended, No. 333-30774, and incorporated herein by
          reference).


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 Securities Act of 1933;

               (ii)  To reflect in the prospectus any facts or events arising
          after the effective date of the Registration Statement (or the most
          recent post-effective amendment thereof) which, individually or in the
          aggregate, represents a fundamental change in the information set
          forth in the Registration Statement.  Notwithstanding the foregoing,
          any increase or decrease in volume of securities offered (if the total
          dollar value of securities offered would not exceed that which was
          registered) and any deviation from the low or high end of the
          estimated maximum offering range may be reflected in the form of
          prospectus filed with the Commission pursuant to Rule 424(b) (Section
          230.424(b) of this chapter) if, in the aggregate, the changes in
          volume and price represent no more than a 20% change in the maximum
          aggregate offering price set forth in the "Calculation of Registration
          Fee" table in the effective Registration Statement.

               (iii) To include any material information with respect to the
          plan of distribution not previously disclosed in the Registration
          Statement or any material change to such information in the
          Registration Statement;

          Provided, however, that paragraphs (a)(1)(i) and (a)(1)(ii) do not
     apply if the Registration Statement is on Form S-3 or Form S-8, and the
     information required to be included in a post-effective amendment by those
     paragraphs is contained in periodic reports filed by the Registrant
     pursuant to Section 13 or Section 15(d) of the Securities Exchange Act of
     1934 that are incorporated by reference in this Registration Statement.

     (2)  That, for the purpose of determining any liability under the
     Securities Act of 1933, each such post-effective amendment shall be deemed
     to be a new registration

                                     II-3
<PAGE>

     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.

     (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 offering.

(b)  The undersigned Registrant hereby undertakes that, for purposes of
     determining any liability under the Securities Act of 1933, each filing of
     the Registrant's annual report pursuant to Section 13(a) or Section 15(d)
     of the Securities Exchange Act of 1934 that is incorporated by reference in
     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 Securities Act
     of 1933 may be permitted to directors, officers and controlling persons of
     the Registrant pursuant to the foregoing provisions, or otherwise, the
     Registrant has been advised that in the opinion of the Securities and
     Exchange Commission such indemnification is against public policy as
     expressed in the 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 Act and will be governed by the final
     adjudication of such issue.

                                     II-4
<PAGE>

                                  SIGNATURES

     Pursuant to the requirements of the Securities Act of 1933, 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 Princeton, New Jersey, on December 31, 2000.

                                  ORCHID BIOSCIENCES, INC.

                                  /s/ Dale R. Pfost
                                  -------------------------------------
                                             Dale R. Pfost,
                                  President and Chief Executive Officer


                               POWER OF ATTORNEY

     Each person whose signature appears below constitutes and appoints Dale R.
Pfost and Donald R. Marvin, and each of them (with full power to act alone) his
true and lawful attorney-in-fact and agent, with full power of substitution and
resubstitution, for him and in his name, place and stead, and in any and all
capacities, to sign any and all amendments (including post-effective amendments)
to this Registration Statement on Form S-8 (and any other registration statement
for the same offering that is to be effective upon filing pursuant to Rule
462(b) under the Securities Act of 1933) of Orchid BioSciences, Inc., and to
file the same, with all exhibits thereto and other documents in connection
therewith, with the Securities and Exchange Commission, granting unto said
attorney-in-fact and agent, full power and authority to do and perform each and
every act and thing requisite or necessary to be done in and about the premises,
as full to all intents and purposes as he might or could do in person, hereby
ratifying and conforming all that said attorney-in-fact and agent or his
substitute and substitutes may lawfully do or cause to be done by virtue hereof.

     Pursuant to the requirements of the Securities Act of 1933, this
registration statement has been signed by the following persons in the
capacities indicated on December 31, 2000.

<TABLE>
<CAPTION>
Signatures                                      Title                                                       Date
----------                                      ------                                                      -----
<S>                                             <C>                                                         <C>
/s/ Dale R. Pfost, Ph.D.                        President, Chief Executive Officer and Director             December 31, 2000
------------------------                        (principal executive officer)
Dale R. Pfost, Ph.D.

/s/ Donald R. Marvin                            Senior Vice President, Chief Operating Officer and Chief    December 31, 2000
--------------------                            Financial Officer (principal financial and accounting
Donald R. Marvin                                officer)


/s/ Sidney M. Hecht, Ph.D.                      Director                                                    December 31, 2000
--------------------------
Sidney M. Hecht, Ph.D.

/s/ Samuel D. Islay                             Director                                                    December 31, 2000
-------------------
Samuel D. Islay

/s/ Jeremy M. Levin, D. Phil., MB. BChair       Director                                                    December 31, 2000
-----------------------------------------
Jeremy M. Levin, D. Phil., MB. BChair

/s/ Anne M. VanLent                             Director                                                    December 31, 2000
-------------------
Anne M. VanLent

/s/ Robert M. Tien, M.D., M.P.H                 Director                                                    December 31, 2000
-------------------------------
Robert M. Tien, M.D., M.P.H.

/s/ Ernest Mario, Ph.D.                         Director                                                    December 31, 2000
-----------------------
Ernest Mario, Ph.D.

/s/ George Poste, DVM, Ph.D.                    Director                                                    December 31, 2000
----------------------------
George Poste, DVM, Ph.D.
</TABLE>
<PAGE>

                           ORCHID BIOSCIENCES, INC.
                         INDEX TO EXHIBITS FILED WITH
                        FORM S-8 REGISTRATION STATEMENT

<TABLE>
<CAPTION>
 Exhibit
 -------
 Number                              Description of Exhibits                                                  Page
 -----            --------------------------------------------------------------------                        ----
<S>         <C>                                                                                               <C>
4.1         --Restated Certificate of Incorporation of the Company (incorporated by reference to
            Exhibit 3.2 to the Registrant's Registration Statement on Form S-1, as amended, No, 333-
            30774, effective May 4, 2000)

4.2         --Bylaws of the Company (incorporated by reference to Exhibit 3.3 to the Registrant's
            Registration Statement on Form S-1, as amended, No, 333-30774, effective May 4, 2000)

4.3         --Specimen Certificate for Shares of Common Stock (incorporated by reference to Exhibit
            4.1 to the Registrant's Registration Statement on Form S-1, as amended, No, 333-30773,
            effective May 4, 2000)

5.1         --Opinion of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. regarding the legality
            of the common stock being registered

23.1        --Consent of KPMG LLP (filed herewith)

23.2        --Consent of KPMG LLP (filed herewith)

23.3        --Consent of Deloitte & Touche LLP (filed herewith)

23.4        --Consent of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. (included in opinion of
            counsel filed as Exhibit 5.1)

24.1        --Powers of Attorney (included in Signature Page)

99.1        --Orchid BioSciences, Inc. 1995 Stock Incentive Plan (Filed as
            Exhibit 10.1 to the Registration Statement on Form S-1, as amended,
            No. 333-30774, and incorporated herein by reference)

99.2        --Orchid BioSciences, Inc. 2000 Employee, Director and Consultant Stock Plan (Filed as
            Exhibit 10.2 to the Registration Statement on Form S-1, as amended, No. 333-30774, and
            incorporated herein by reference)
</TABLE>
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{"company-data": {"conformed-name": "ORCHID BIOSCIENCES INC", "cik": "0001107216", "assigned-sic": "8731", "irs-number": "223392819"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-53118", "film-number": "1500860"}, "business-address": {"street1": "303 COLLEGE RD. EAST", "city": "PRINCETON", "state": "NJ", "zip": "08540", "phone": "6097502200"}, "mail-address": {"street1": "303 COLLEGE RD. EAST", "city": "PRINCETON", "state": "NJ", "zip": "08540"}}
As filed with the Securities and Exchange Commission on January 3, 2001
                                                          REGISTRATION NO. 333 -
================================================================================

                      SECURITIES AND EXCHANGE COMMISSION
                            WASHINGTON, D.C. 20549

                                   FORM S-8
                            REGISTRATION STATEMENT
                                   under the
                            SECURITIES ACT OF 1933

                           ORCHID BIOSCIENCES, INC.
            (Exact name of Registrant as specified in its charter)

             Delaware                                    22-3392819
    (State or other jurisdiction                      (I.R.S. Employer
  of incorporation or organization)                 Identification No.)

                             303 College Road East
                              Princeton, NJ 08540
                                (609) 750-2200
                   (Address of Principal Executive Offices)

                           ORCHID BIOSCIENCES, INC.
                           1995 STOCK INCENTIVE PLAN

                           ORCHID BIOSCIENCES, INC.
                          2000 EMPLOYEE, DIRECTOR AND
                             CONSULTANT STOCK PLAN
                           (Full title of the plan)

                             Dale R. Pfost, Ph.D.
                           ORCHID BIOSCIENCES, INC.
                             303 College Road East
                              Princeton, NJ 08540
                                (609) 750-2200
(Name, address, including zip code, and telephone number, including area code,
                             of agent for service)
CALCULATION OF REGISTRATION FEE
===========================================================================================================================
 Title of securities       Amount to be        Proposed Maximum offering     Proposed Maximum aggregate       Amount of
  to be registered        registered/(1)/         price per share/(2)/           offering price/(2)/       registration fee
---------------------------------------------------------------------------------------------------------------------------
Common Stock, par value     3,581,351                   $6.218                     $22,268,841                $5,567.21
$0.001 per share            1,418,649                   $8.000                     $11,349,192                $2,837.30
                            ---------                                                                        ----------
                            5,000,000                                                                         $8,404.51
===========================================================================================================================
(1) The number of shares of common stock, par value $0.001 per share (the
    "Common Stock"), stated above consists of the aggregate number of shares
    which may be sold upon the exercise of options (i) which have been granted
    and which are currently outstanding and (ii) which may hereafter be granted,
    under the Orchid BioSciences, Inc. 1995 Stock Incentive Plan and the Orchid
    BioSciences, Inc. 2000 Employee, Director and Consultant Stock Plan (the
    "Plans") and which have not been previously registered under the Securities
    Act of 1933, as amended (the "Securities Act").  The maximum number of
    shares which may be sold upon the exercise of such options granted under the
    Plans is subject to adjustment in accordance with certain anti-dilution and
    other provisions of the Plans.  Accordingly, pursuant to Rule 416 under the
    Securities Act, this Registration Statement covers, in addition to the
    number of shares stated above, an indeterminate number of shares which may
    be subject to grant or otherwise issuable after the operation of any such
    anti-dilution and other provisions.

(2) This calculation is made solely for the purpose of determining the
    registration fee pursuant to the provisions of Rule 457(h) under the
    Securities Act as follows: (i) in the case of shares of Common Stock which
    may be purchased upon exercise of outstanding options, the fee is calculated
    on the basis of the price at which options may be exercised; and (ii) in the
    case of shares of Common Stock for which options have not yet been granted
    and the option price of which is therefore unknown, the fee is calculated on
    the basis of the average of the high and low sale prices per share of Common
    Stock on the Nasdaq National Market as of a date (December 22, 2000) within
    5 business days prior to filing this Registration Statement.

________________________________________________________________________________
EXPLANATORY NOTE
                               ----------------

     In accordance with the instructional Note to Part I of Form S-8 as
promulgated by the Securities and Exchange Commission, the information specified
by Part I of Form S-8 has been omitted from this Registration Statement on Form
S-8 for offers of shares of Common Stock pursuant to the Plans.
PART II

              INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

Item 3.  Incorporation of Certain Documents by Reference.
--------------------------------------------------------

     The following documents filed by the Registrant with the Commission are
incorporated herein by reference:

     (a) Our prospectus filed pursuant to Rule 424(b) under the Securities Act
  of 1933, as amended, containing our audited financial statements for the
  fiscal year ended December 31, 1999, filed on May 4, 2000;

     (b) Our report on Form 10-Q/A for the quarterly period ended March 31,
  2000, filed on August 10, 2000, our report on Form 10-Q for the quarterly
  period ended June 30, 2000, filed on August 15, 2000, and our report on Form
  10-Q for the quarterly period ended September 30, 2000 filed on November 14,
  2000; and

     (c) The description of the Common Stock contained in the our Registration
  Statement on Form 8-A filed under the Securities Exchange Act of 1934,
  including any amendment or report filed for the purpose of updating such
  description.

     All reports and other documents filed by the Registrant after the date
hereof pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Securities
Exchange Act of 1934 prior to the filing of a post-effective amendment which
indicates that all securities offered hereby have been sold or which deregisters
all securities then remaining unsold, shall be deemed to be incorporated by
reference herein and to be part hereof from the date of filing of such reports
and documents.

Item 4.  Description of Securities.
----------------------------------

     Not applicable.

Item 5.  Interests of Named Experts and Counsel.
-----------------------------------------------

     This Registration Statement was prepared for us by Mintz, Levin, Cohn,
Ferris, Glovsky and Popeo, P.C., Boston, Massachusetts. Attorneys at Mintz Levin
own an aggregate of 604 shares of Common Stock.
Item 6.  Indemnification of Directors and Officers.
     --------------------------------------------------

     Incorporated herein by reference from Registration Statement on Form S-1,
No. 333-30774.

Item 7.  Exemption from Registration Claimed.
--------------------------------------------

     Not applicable.

Item 8.  Exhibits.
-----------------

 Exhibit
 -------
  Number                       Description of Exhibits
  ------        -------------------------------------------------------

4.1       --Restated Certificate of Incorporation of the Company (incorporated
          by reference to Exhibit 3.2 to the Registrant's Registration Statement
          on Form S-1, as amended, No, 333-30774, effective May 4, 2000).

4.2       --Bylaws of the Company (incorporated by reference to Exhibit 3.3 to
          the Registrant's Registration Statement on Form S-1, as amended, No,
          333-30774, effective May 4, 2000).

4.3       --Specimen Certificate for Shares of Common Stock (incorporated by
          reference to Exhibit 4.1 to the Registrant's Registration Statement on
          Form S-1, as amended, No, 333-30773, effective May 4, 2000).

5.1       --Opinion of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
          regarding the legality of the common stock being registered.

23.1      --Consent of KPMG LLP (filed herewith).

23.2      --Consent of KPMG LLP (filed herewith).

23.3      --Consent of Deloitte & Touche LLP (filed herewith).

23.4      --Consent of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
          (included in opinion of counsel filed as Exhibit 5.1).

24.1      --Powers of Attorney (included in Signature Page).

99.1      --Orchid BioSciences, Inc. 1995 Stock Incentive Plan (Filed as Exhibit
          10.1 to the Registration Statement on Form S-1, as amended, No. 333-
          30774, and incorporated herein by reference).

                                     II-2
99.2      --Orchid BioSciences, Inc. 2000 Employee, Director and Consultant
          Stock Plan (Filed as Exhibit 10.2 to the Registration Statement on
          Form S-1, as amended, No. 333-30774, and incorporated herein by
          reference).

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 Securities Act of 1933;

               (ii)  To reflect in the prospectus any facts or events arising
          after the effective date of the Registration Statement (or the most
          recent post-effective amendment thereof) which, individually or in the
          aggregate, represents a fundamental change in the information set
          forth in the Registration Statement.  Notwithstanding the foregoing,
          any increase or decrease in volume of securities offered (if the total
          dollar value of securities offered would not exceed that which was
          registered) and any deviation from the low or high end of the
          estimated maximum offering range may be reflected in the form of
          prospectus filed with the Commission pursuant to Rule 424(b) (Section
          230.424(b) of this chapter) if, in the aggregate, the changes in
          volume and price represent no more than a 20% change in the maximum
          aggregate offering price set forth in the "Calculation of Registration
          Fee" table in the effective Registration Statement.

               (iii) To include any material information with respect to the
          plan of distribution not previously disclosed in the Registration
          Statement or any material change to such information in the
          Registration Statement;

          Provided, however, that paragraphs (a)(1)(i) and (a)(1)(ii) do not
     apply if the Registration Statement is on Form S-3 or Form S-8, and the
     information required to be included in a post-effective amendment by those
     paragraphs is contained in periodic reports filed by the Registrant
     pursuant to Section 13 or Section 15(d) of the Securities Exchange Act of
     1934 that are incorporated by reference in this Registration Statement.

     (2)  That, for the purpose of determining any liability under the
     Securities Act of 1933, each such post-effective amendment shall be deemed
     to be a new registration

                                     II-3
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.

     (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 offering.

(b)  The undersigned Registrant hereby undertakes that, for purposes of
     determining any liability under the Securities Act of 1933, each filing of
     the Registrant's annual report pursuant to Section 13(a) or Section 15(d)
     of the Securities Exchange Act of 1934 that is incorporated by reference in
     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 Securities Act
     of 1933 may be permitted to directors, officers and controlling persons of
     the Registrant pursuant to the foregoing provisions, or otherwise, the
     Registrant has been advised that in the opinion of the Securities and
     Exchange Commission such indemnification is against public policy as
     expressed in the 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 Act and will be governed by the final
     adjudication of such issue.

                                     II-4
SIGNATURES

     Pursuant to the requirements of the Securities Act of 1933, 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 Princeton, New Jersey, on December 31, 2000.

                                  ORCHID BIOSCIENCES, INC.

                                  /s/ Dale R. Pfost
                                  -------------------------------------
                                             Dale R. Pfost,
                                  President and Chief Executive Officer

                               POWER OF ATTORNEY

     Each person whose signature appears below constitutes and appoints Dale R.
Pfost and Donald R. Marvin, and each of them (with full power to act alone) his
true and lawful attorney-in-fact and agent, with full power of substitution and
resubstitution, for him and in his name, place and stead, and in any and all
capacities, to sign any and all amendments (including post-effective amendments)
to this Registration Statement on Form S-8 (and any other registration statement
for the same offering that is to be effective upon filing pursuant to Rule
462(b) under the Securities Act of 1933) of Orchid BioSciences, Inc., and to
file the same, with all exhibits thereto and other documents in connection
therewith, with the Securities and Exchange Commission, granting unto said
attorney-in-fact and agent, full power and authority to do and perform each and
every act and thing requisite or necessary to be done in and about the premises,
as full to all intents and purposes as he might or could do in person, hereby
ratifying and conforming all that said attorney-in-fact and agent or his
substitute and substitutes may lawfully do or cause to be done by virtue hereof.

     Pursuant to the requirements of the Securities Act of 1933, this
registration statement has been signed by the following persons in the
capacities indicated on December 31, 2000.
Signatures                                      Title                                                       Date
----------                                      ------                                                      -----
/s/ Dale R. Pfost, Ph.D.                        President, Chief Executive Officer and Director             December 31, 2000
------------------------                        (principal executive officer)
Dale R. Pfost, Ph.D.

/s/ Donald R. Marvin                            Senior Vice President, Chief Operating Officer and Chief    December 31, 2000
--------------------                            Financial Officer (principal financial and accounting
Donald R. Marvin                                officer)

/s/ Sidney M. Hecht, Ph.D.                      Director                                                    December 31, 2000
--------------------------
Sidney M. Hecht, Ph.D.

/s/ Samuel D. Islay                             Director                                                    December 31, 2000
-------------------
Samuel D. Islay

/s/ Jeremy M. Levin, D. Phil., MB. BChair       Director                                                    December 31, 2000
-----------------------------------------
Jeremy M. Levin, D. Phil., MB. BChair

/s/ Anne M. VanLent                             Director                                                    December 31, 2000
-------------------
Anne M. VanLent

/s/ Robert M. Tien, M.D., M.P.H                 Director                                                    December 31, 2000
-------------------------------
Robert M. Tien, M.D., M.P.H.

/s/ Ernest Mario, Ph.D.                         Director                                                    December 31, 2000
-----------------------
Ernest Mario, Ph.D.

/s/ George Poste, DVM, Ph.D.                    Director                                                    December 31, 2000
----------------------------
George Poste, DVM, Ph.D.
ORCHID BIOSCIENCES, INC.
                         INDEX TO EXHIBITS FILED WITH
                        FORM S-8 REGISTRATION STATEMENT
Exhibit
 -------
 Number                              Description of Exhibits                                                  Page
 -----            --------------------------------------------------------------------                        ----
4.1         --Restated Certificate of Incorporation of the Company (incorporated by reference to
            Exhibit 3.2 to the Registrant's Registration Statement on Form S-1, as amended, No, 333-
            30774, effective May 4, 2000)

4.2         --Bylaws of the Company (incorporated by reference to Exhibit 3.3 to the Registrant's
            Registration Statement on Form S-1, as amended, No, 333-30774, effective May 4, 2000)

4.3         --Specimen Certificate for Shares of Common Stock (incorporated by reference to Exhibit
            4.1 to the Registrant's Registration Statement on Form S-1, as amended, No, 333-30773,
            effective May 4, 2000)

5.1         --Opinion of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. regarding the legality
            of the common stock being registered

23.1        --Consent of KPMG LLP (filed herewith)

23.2        --Consent of KPMG LLP (filed herewith)

23.3        --Consent of Deloitte & Touche LLP (filed herewith)

23.4        --Consent of Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. (included in opinion of
            counsel filed as Exhibit 5.1)

24.1        --Powers of Attorney (included in Signature Page)

99.1        --Orchid BioSciences, Inc. 1995 Stock Incentive Plan (Filed as
            Exhibit 10.1 to the Registration Statement on Form S-1, as amended,
            No. 333-30774, and incorporated herein by reference)

99.2        --Orchid BioSciences, Inc. 2000 Employee, Director and Consultant Stock Plan (Filed as
            Exhibit 10.2 to the Registration Statement on Form S-1, as amended, No. 333-30774, and
            incorporated herein by reference)