<PAGE>   1

     As filed with the Securities and Exchange Commission on March 4, 1998


                       SECURITIES AND EXCHANGE COMMISSION

                             WASHINGTON, D.C. 20549

                                   ----------

                                    FORM S-8
                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                          MEDICAL SCIENCE SYSTEMS, INC.
             (Exact name of registrant as specified in its charter)

             TEXAS                                     94-3123681
(State or other jurisdiction of            (I.R.S. Employer Identification No.)
 incorporation or organization)


                       4400 MACARTHUR BOULEVARD, SUITE 980
                         NEWPORT BEACH, CALIFORNIA 92660
                (Address of Principal Executive Office)(Zip Code)

                           1996 EQUITY INCENTIVE PLAN
                            (full title of the plan)

                                  PAUL J. WHITE
                       4400 MACARTHUR BOULEVARD, SUITE 980
                         NEWPORT BEACH, CALIFORNIA 92660
                     (Name and address of agent for service)

                                 (714) 440-9730
          (Telephone number, including area code, of agent for service)

                                   ----------

                         CALCULATION OF REGISTRATION FEE



<TABLE>
<CAPTION>
===========================================================================================================
                                                  PROPOSED MAXIMUM     PROPOSED MAXIMUM
            TITLE OF              AMOUNT TO BE   OFFERING PRICE PER    AGGREGATE OFFERING    AMOUNT OF
  SECURITIES TO BE REGISTERED      REGISTERED         SHARE(1)             PRICE(1)        REGISTRATION FEE
-----------------------------------------------------------------------------------------------------------
<S>                               <C>                <C>                 <C>                 <C>           
Common Stock, no par value......    1,300,000          $4.72              $6,136,000          $1,810
===========================================================================================================
</TABLE>
(1) Estimated solely for the purpose of calculating the registration fee
    pursuant to Rule 457 (c) and (h)(1), based on the closing price of the
    Company's Common Stock.


Exhibit index is located at sequentially paginated page number 5.    Page 1 of 7

<PAGE>   2

                                     PART I

                           INFORMATION REQUIRED IN THE
                            SECTION 10(a) PROSPECTUS

        The documents containing the information specified in Part I (plan
information and registrant information) will be sent or given to employees as
specified by Rule 428(b)(1). Such documents need not be filed with the
Securities and Exchange Commission either as part of this Registration Statement
or as prospectuses or prospectus supplements pursuant to Rule 424. These
documents and the documents incorporated by reference in this Registration
Statement pursuant to Item 3 of Part II of this form, taken together, constitute
a prospectus that meets the requirements of Section 10(a) of the Securities Act
of 1933.


                                        2

<PAGE>   3

                                     PART II

                           INFORMATION REQUIRED IN THE
                             REGISTRATION STATEMENT

ITEM 3. INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE.

        The following documents of Medical Science Systems, Inc., a Texas
corporation (the "Company"), previously filed with the Commission are
incorporated herein by reference:

        1.     Prospectus filed pursuant to Rule 424b5 (File No. 333-37441)
               filed on December 1, 1997 (the "Prospectus")

        2.     The Registrant's Registration Statement on Form 8-A (File No.
               000-23413) filed on November 24, 1997, as amended by Amendment
               No. 1 filed on November 25, 1997, and Amendment No.
               2 filed on December 15, 1997.

        In addition, all documents subsequently filed by the Company pursuant to
Sections 13(a), 13(c), 14 or 15(d) of the Securities and Exchange Act of 1934
(the "Exchange Act") 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 into the prospectus and to be a part hereof from the date of filing of
such documents.


ITEM 4. DESCRIPTION OF SECURITIES.

        The Common Stock of the Company, no par value (the "Common Stock") is
registered pursuant to Section 12 of the Exchange Act, and, therefore, the
description of securities is omitted.


ITEM 5. INTERESTS OF NAMED EXPERTS AND COUNSEL.

        None.


ITEM 6. INDEMNIFICATION OF DIRECTORS AND OFFICERS.

        As allowed by Texas Revised Statutes, the Bylaws of the Company provide
that the liability of the directors and executive officers of the Company for
monetary damages shall be eliminated to the fullest extent permissible under
Texas law. The right to indemnification extends to any such director or
executive officer even though such director or executive officer is or was
serving at the request of the Company as a director, officer, partner, venturer,
proprietor, trustee, employee, agent or similar functionary of another foreign
or domestic corporation, partnership, joint venture, sole proprietorship, trust,
employee benefit plan or other enterprise. The Bylaws of the Company further
provide that any other officer may be indemnified to the same extent by duly
adopted resolution of the Board of Directors. Additionally, the indemnification
rights provided in the Bylaws are not exclusive and the Company, its directors
and its shareholders are expressly permitted to approve or enter, and have
approved or have entered into, contractual or other arrangements with the
Company's directors and officers that provide to such directors and officers the
same or similar indemnification rights or related provisions meant to facilitate
their receipt of such benefits or such other indemnification provisions as may
be deemed appropriate. All such provisions related to indemnification are
intended to eliminate the personal liability of a director or officer for
monetary damages in an action brought by or in the right of the Company for
breach of such director's or officer's duties to the Company or its shareholders
except for liability for acts or omissions that involve intentional misconduct
or knowing and culpable violation of law, for acts or omissions that such
director or officer believes to be contrary the best interests of the Company or
its shareholders or that involve the absence

                                              3

<PAGE>   4

of good faith on the part of the director, for any transaction from which a
director derived an improper personal benefit, for acts or omissions that show a
reckless disregard for the director's or officer's duty to the Company or its
shareholders in circumstances in which the director or officer was aware, or
should have been aware, in the ordinary course of performing a director's or
officer's duties, of a risk of serious injury to the Company or its
shareholders, for acts or omissions that constitute an unexcused pattern of
inattention that amounts to an abdication of the director's or officer's duty to
the Company or its shareholders, with respect to certain contracts in which a
director or officer has a material financial interest and for approval of
certain improper distributions to shareholders or certain loans or guarantees.
This provision does not limit or eliminate the rights of the Company or any
shareholder to seek non-monetary relief such as an injunction or rescission in
the event of a breach of a director's or officer's duty of care.


ITEM 7. EXEMPTION FROM REGISTRATION CLAIMED.

        Not applicable.


ITEM 8. EXHIBITS.

        See Exhibit Index appearing at sequentially numbered page 5.


ITEM 9. UNDERTAKINGS.

        The undersigned registrant hereby undertakes:

(b) The undersigned registrant hereby undertakes that, for purposes of
determining any liability under the Securities Act, each filing of the
registrant's annual report pursuant to Section 13(a) or Section 15(d) of the
Exchange Act (and, where applicable, each filing of an employee benefit plan's
annual report pursuant to Section 15(d) of the Exchange Act) that is
incorporated by reference in the 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.

(h) Insofar as indemnification for liabilities arising under the Securities Act
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 Securities Act and will be governed by the final
adjudication of such issue.


                                        4

<PAGE>   5

                                  EXHIBIT INDEX

<TABLE>
<CAPTION>
EXHIBIT                                                                    SEQUENTIAL
NUMBER       DESCRIPTION                                                    PAGE NO.
------       -----------                                                    --------
<C>          <S>                                                             <C>   
   4.1 *     1996 Equity Incentive Plan of Medical Science Systems, Inc.,
             adopted as of June 28, 1996, together with amendment thereto
             dated May 6, 1997.

   4.2 *     Medical Science Systems, Inc., 1996 Equity Incentive Plan
             Stock Option Agreement.

   4.3 *     Medical Science Systems, Inc. 1996 Equity Incentive Plan
             Stock Option Exercise Agreement.

   5.1       Opinion of Jeffers, Wilson, Shaff & Falk, LLP.                     

  23.1       Consent of Singer Lewak Greenbaum & Goldstein LLP.                 

  23.2       Consent of Jeffers, Wilson & Shaff & Falk, LLP                     
             (included in Exhibit 5.1).

  24.1       Power of Attorney.                                                
</TABLE>
--------------
*    Previously filed as Exhibits to Registration Statement File No. 333-37441.


                                        5

<PAGE>   6

                                   SIGNATURES

        THE REGISTRANT. 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 Newport Beach, State of California, on February
27, 1998.


                                    MEDICAL SCIENCE SYSTEMS, INC.


                                    By: /s/ Paul J. White
                                        ----------------------------------------
                                            Paul J. White, President
                                            (principle executive officer)

        Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed below by the following persons in the
capacities and on the date indicated.


<TABLE>
<CAPTION>
Signatures                               Title                                  Date
----------                               -----                                  ----
<S>                                      <C>                                    <C>              


/s/ Paul J. White                        Chief Executive Officer                February 27, 1998
----------------------------------       and Chairman of the Board
Paul J. White                            


/s/ Michael Newman                       Executive Vice President and           February 27, 1998
----------------------------------       Secretary, and Director
Michael Newman                     


/s/ U. Spencer Allen                     Chief Financial Officer                February 27, 1998
----------------------------------       (principal Accounting Officer)
U. Spencer Allen                   


/s/ Ronald L. La Rosa                    Director                               February 27, 1998
----------------------------------
Ronald L. La Rosa
</TABLE>


                                        6
[{"type": "S-8", "sequence": "1", "description": "FORM S-8", "secsgml_size_bytes": 13623}]
{"company-data": {"conformed-name": "MEDICAL SCIENCE SYSTEMS INC", "cik": "0001037649", "assigned-sic": "8071", "irs-number": "943123681", "state-of-incorporation": "TX", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-47343", "film-number": "98557686"}, "business-address": {"street1": "4400 MACARTHUR BLVD", "street2": "STE 980", "city": "NEWPORT BEACH", "state": "CA", "zip": "92660-2031", "phone": "7144409730"}, "mail-address": {"street1": "4400 MACARTHUR BLVD", "street2": "STE 980", "city": "NEWPORT BEACH", "state": "CA", "zip": "92660-2031"}}
1

     As filed with the Securities and Exchange Commission on March 4, 1998

                       SECURITIES AND EXCHANGE COMMISSION

                             WASHINGTON, D.C. 20549

                                   ----------

                                    FORM S-8
                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                          MEDICAL SCIENCE SYSTEMS, INC.
             (Exact name of registrant as specified in its charter)

             TEXAS                                     94-3123681
(State or other jurisdiction of            (I.R.S. Employer Identification No.)
 incorporation or organization)

                       4400 MACARTHUR BOULEVARD, SUITE 980
                         NEWPORT BEACH, CALIFORNIA 92660
                (Address of Principal Executive Office)(Zip Code)

                           1996 EQUITY INCENTIVE PLAN
                            (full title of the plan)

                                  PAUL J. WHITE
                       4400 MACARTHUR BOULEVARD, SUITE 980
                         NEWPORT BEACH, CALIFORNIA 92660
                     (Name and address of agent for service)

                                 (714) 440-9730
          (Telephone number, including area code, of agent for service)

                                   ----------

                         CALCULATION OF REGISTRATION FEE
===========================================================================================================
                                                  PROPOSED MAXIMUM     PROPOSED MAXIMUM
            TITLE OF              AMOUNT TO BE   OFFERING PRICE PER    AGGREGATE OFFERING    AMOUNT OF
  SECURITIES TO BE REGISTERED      REGISTERED         SHARE(1)             PRICE(1)        REGISTRATION FEE
-----------------------------------------------------------------------------------------------------------
Common Stock, no par value......    1,300,000          $4.72              $6,136,000          $1,810
===========================================================================================================
(1) Estimated solely for the purpose of calculating the registration fee
    pursuant to Rule 457 (c) and (h)(1), based on the closing price of the
    Company's Common Stock.

Exhibit index is located at sequentially paginated page number 5.    Page 1 of 7
2

                                     PART I

                           INFORMATION REQUIRED IN THE
                            SECTION 10(a) PROSPECTUS

        The documents containing the information specified in Part I (plan
information and registrant information) will be sent or given to employees as
specified by Rule 428(b)(1). Such documents need not be filed with the
Securities and Exchange Commission either as part of this Registration Statement
or as prospectuses or prospectus supplements pursuant to Rule 424. These
documents and the documents incorporated by reference in this Registration
Statement pursuant to Item 3 of Part II of this form, taken together, constitute
a prospectus that meets the requirements of Section 10(a) of the Securities Act
of 1933.

                                        2
3

                                     PART II

                           INFORMATION REQUIRED IN THE
                             REGISTRATION STATEMENT

ITEM 3. INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE.

        The following documents of Medical Science Systems, Inc., a Texas
corporation (the "Company"), previously filed with the Commission are
incorporated herein by reference:

        1.     Prospectus filed pursuant to Rule 424b5 (File No. 333-37441)
               filed on December 1, 1997 (the "Prospectus")

        2.     The Registrant's Registration Statement on Form 8-A (File No.
               000-23413) filed on November 24, 1997, as amended by Amendment
               No. 1 filed on November 25, 1997, and Amendment No.
               2 filed on December 15, 1997.

        In addition, all documents subsequently filed by the Company pursuant to
Sections 13(a), 13(c), 14 or 15(d) of the Securities and Exchange Act of 1934
(the "Exchange Act") 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 into the prospectus and to be a part hereof from the date of filing of
such documents.

ITEM 4. DESCRIPTION OF SECURITIES.

        The Common Stock of the Company, no par value (the "Common Stock") is
registered pursuant to Section 12 of the Exchange Act, and, therefore, the
description of securities is omitted.

ITEM 5. INTERESTS OF NAMED EXPERTS AND COUNSEL.

        None.

ITEM 6. INDEMNIFICATION OF DIRECTORS AND OFFICERS.

        As allowed by Texas Revised Statutes, the Bylaws of the Company provide
that the liability of the directors and executive officers of the Company for
monetary damages shall be eliminated to the fullest extent permissible under
Texas law. The right to indemnification extends to any such director or
executive officer even though such director or executive officer is or was
serving at the request of the Company as a director, officer, partner, venturer,
proprietor, trustee, employee, agent or similar functionary of another foreign
or domestic corporation, partnership, joint venture, sole proprietorship, trust,
employee benefit plan or other enterprise. The Bylaws of the Company further
provide that any other officer may be indemnified to the same extent by duly
adopted resolution of the Board of Directors. Additionally, the indemnification
rights provided in the Bylaws are not exclusive and the Company, its directors
and its shareholders are expressly permitted to approve or enter, and have
approved or have entered into, contractual or other arrangements with the
Company's directors and officers that provide to such directors and officers the
same or similar indemnification rights or related provisions meant to facilitate
their receipt of such benefits or such other indemnification provisions as may
be deemed appropriate. All such provisions related to indemnification are
intended to eliminate the personal liability of a director or officer for
monetary damages in an action brought by or in the right of the Company for
breach of such director's or officer's duties to the Company or its shareholders
except for liability for acts or omissions that involve intentional misconduct
or knowing and culpable violation of law, for acts or omissions that such
director or officer believes to be contrary the best interests of the Company or
its shareholders or that involve the absence

                                              3
4

of good faith on the part of the director, for any transaction from which a
director derived an improper personal benefit, for acts or omissions that show a
reckless disregard for the director's or officer's duty to the Company or its
shareholders in circumstances in which the director or officer was aware, or
should have been aware, in the ordinary course of performing a director's or
officer's duties, of a risk of serious injury to the Company or its
shareholders, for acts or omissions that constitute an unexcused pattern of
inattention that amounts to an abdication of the director's or officer's duty to
the Company or its shareholders, with respect to certain contracts in which a
director or officer has a material financial interest and for approval of
certain improper distributions to shareholders or certain loans or guarantees.
This provision does not limit or eliminate the rights of the Company or any
shareholder to seek non-monetary relief such as an injunction or rescission in
the event of a breach of a director's or officer's duty of care.

ITEM 7. EXEMPTION FROM REGISTRATION CLAIMED.

        Not applicable.

ITEM 8. EXHIBITS.

        See Exhibit Index appearing at sequentially numbered page 5.

ITEM 9. UNDERTAKINGS.

        The undersigned registrant hereby undertakes:

(b) The undersigned registrant hereby undertakes that, for purposes of
determining any liability under the Securities Act, each filing of the
registrant's annual report pursuant to Section 13(a) or Section 15(d) of the
Exchange Act (and, where applicable, each filing of an employee benefit plan's
annual report pursuant to Section 15(d) of the Exchange Act) that is
incorporated by reference in the 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.

(h) Insofar as indemnification for liabilities arising under the Securities Act
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 Securities Act and will be governed by the final
adjudication of such issue.

                                        4
5

                                  EXHIBIT INDEX
EXHIBIT                                                                    SEQUENTIAL
NUMBER       DESCRIPTION                                                    PAGE NO.
------       -----------                                                    --------
4.1 *     1996 Equity Incentive Plan of Medical Science Systems, Inc.,
             adopted as of June 28, 1996, together with amendment thereto
             dated May 6, 1997.

   4.2 *     Medical Science Systems, Inc., 1996 Equity Incentive Plan
             Stock Option Agreement.

   4.3 *     Medical Science Systems, Inc. 1996 Equity Incentive Plan
             Stock Option Exercise Agreement.

   5.1       Opinion of Jeffers, Wilson, Shaff & Falk, LLP.                     

  23.1       Consent of Singer Lewak Greenbaum & Goldstein LLP.                 

  23.2       Consent of Jeffers, Wilson & Shaff & Falk, LLP                     
             (included in Exhibit 5.1).

  24.1       Power of Attorney.
--------------
*    Previously filed as Exhibits to Registration Statement File No. 333-37441.

                                        5
6

                                   SIGNATURES

        THE REGISTRANT. 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 Newport Beach, State of California, on February
27, 1998.

                                    MEDICAL SCIENCE SYSTEMS, INC.

                                    By: /s/ Paul J. White
                                        ----------------------------------------
                                            Paul J. White, President
                                            (principle executive officer)

        Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed below by the following persons in the
capacities and on the date indicated.
Signatures                               Title                                  Date
----------                               -----                                  ----
/s/ Paul J. White                        Chief Executive Officer                February 27, 1998
----------------------------------       and Chairman of the Board
Paul J. White                            

/s/ Michael Newman                       Executive Vice President and           February 27, 1998
----------------------------------       Secretary, and Director
Michael Newman                     

/s/ U. Spencer Allen                     Chief Financial Officer                February 27, 1998
----------------------------------       (principal Accounting Officer)
U. Spencer Allen                   

/s/ Ronald L. La Rosa                    Director                               February 27, 1998
----------------------------------
Ronald L. La Rosa
6