<PAGE>   1

     AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON APRIL 9, 2001

                                                   REGISTRATION NO. 333-
================================================================================

                       SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549

                                    FORM S-8

                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                                  ZONAGEN, INC.
             (EXACT NAME OF REGISTRANT AS SPECIFIED IN ITS CHARTER)

                  DELAWARE                                   76-0233274
       (STATE OR OTHER JURISDICTION OF                    (I.R.S. EMPLOYER
       INCORPORATION OR ORGANIZATION)                    IDENTIFICATION NO.)

      2408 TIMBERLOCH PLACE, SUITE B-4
            THE WOODLANDS, TEXAS                                77380
   (ADDRES OF PRINCIPAL EXECUTIVE OFFICES)                    (ZIP CODE)

                  2000 NONEMPLOYEE DIRECTORS' STOCK OPTION PLAN
                        2000 EMPLOYEE STOCK PURCHASE PLAN
                            (FULL TITLE OF THE PLANS)

                               JOSEPH S. PODOLSKI
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                        2408 TIMBERLOCH PLACE, SUITE B-4
                           THE WOODLANDS, TEXAS 77380
                     (NAME AND ADDRESS OF AGENT FOR SERVICE)
                                 (281) 719-3400
          (TELEPHONE NUMBER, INCLUDING AREA CODE, OF AGENT FOR SERVICE)

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

                                    COPY TO:
                             JEFFREY R. HARDER, ESQ.
                             ANDREWS & KURTH L.L.P.
                        2170 BUCKTHORNE PLACE, SUITE 150
                           THE WOODLANDS, TEXAS 77380
                                 (713) 220-4801

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

                         CALCULATION OF REGISTRATION FEE
<TABLE>
<CAPTION>
===================================================================================================================

                                                                                    PROPOSED MAXIMUM
                                                  AMOUNT         PROPOSED MAXIMUM       AGGREGATE       AMOUNT OF
                                                  TO BE           OFFERING PRICE     OFFERING PRICE    REGISTRATION
       TITLE OF PLAN TO BE REGISTERED          REGISTERED(1)      PER SHARE (2)            (2)             FEE
===================================================================================================================
<S>                                            <C>               <C>                <C>                <C>
2000 Nonemployee Directors' Stock Option
  Plan                                         500,000 shares         $2.81            $1,405,000        $351.25
-------------------------------------------------------------------------------------------------------------------
2000 Employee Stock Purchase Plan              150,000 shares         $2.81             $421,500         $105.38
===================================================================================================================
</TABLE>

(1) Pursuant to Rule 416 of the Securities Act, this number includes an
    indeterminate number of additional shares that may be issued under the
    above-referenced plans as a result of anti-dilution provisions, stock
    splits, stock dividends or similar transactions.

(2) Estimated solely for the purpose of calculating the registration fee
    pursuant to Rule 457(c) and (h), based upon the average of the high and low
    sales prices per share of the Registrant's Common Stock reported on The
    Nasdaq National Market on April 3, 2001.

================================================================================
<PAGE>   2

                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

ITEM 3.  INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE.

         Zonagen, Inc. (the "Company") incorporates herein by reference the
following documents as of their respective dates as filed with the Securities
and Exchange Commission (the "Commission"):

                  (a) The Company's Annual Report on Form 10-K (File No.
0-21198) for the year ended December 31, 2000;

                  (b) The description of the Company's common stock, par value
$0.001 per share (the "Common Stock"), contained in the Company's Registration
Statement on Form 8-A filed with the Commission on February 2, 1993, as amended
by Amendment No. 1 thereto filed with the Commission on February 12, 1993 and
Amendment No. 2 thereto filed with the Commission on March 25, 1993.

         All documents filed by the Company pursuant to Section 13(a), 13(c), 14
and 15(d) of the Securities Exchange Act of 1934, as amended (the "Exchange
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 deregisters all such securities then remaining unsold
shall be deemed to be incorporated by reference in this Registration Statement
and to be a part hereof from the date of filing such documents.

ITEM 4.  DESCRIPTION OF SECURITIES.

         The information required by Item 4 is not applicable to this
Registration Statement because the class of securities to be offered is
registered under Section 12 of the Exchange Act.

ITEM 5.  INTERESTS OF NAMED EXPERTS AND COUNSEL.

         The information required by Item 5 is not applicable to this
Registration Statement.

ITEM 6.  INDEMNIFICATION OF DIRECTORS AND OFFICERS.

         Section 145 of the Delaware General Corporation Law ("DGCL"), inter
alia, empowers a Delaware corporation to indemnify any person who was or is a
party or is threatened to be made a party to any threatened, pending or
completed action, suit or proceeding (other than an action by or in the right of
the corporation) by reason of the fact that such person is or was a director,
officer, employee or agent of the corporation, or is or was serving at the
request of the corporation as a director, officer, employee or agent of another
corporation or other enterprise, against expenses (including attorneys' fees),
judgments, fines and amounts paid in settlement actually and reasonably incurred
by him in connection with such action, suit or proceeding if he

                                      II-1
<PAGE>   3

acted in good faith and in a manner he reasonably believed to be in or not
opposed to the best interests of the corporation, and, with respect to any
criminal action or proceeding, had no reasonable cause to believe his conduct
was unlawful. Similar indemnity is authorized for such persons against expenses
(including attorneys' fees) actually and reasonably incurred in connection with
the defense or settlement of any such threatened, pending or completed action or
suit if such person acted in good faith and in a manner he reasonably believed
to be in or not opposed to the best interests of the corporation, and provided
further that (unless a court of competent jurisdiction otherwise provides) such
person shall not have been adjudged liable to the corporation. Any such
indemnification may be made only as authorized in each specific case upon a
determination by the stockholders or disinterested directors or by independent
legal counsel in a written opinion that indemnification is proper because the
indemnitee has met the applicable standard of conduct.

         Section 145 further authorizes a corporation to purchase and maintain
insurance on behalf of any person who is or was a director, officer, employee or
agent of the corporation, or is or was serving at the request of the corporation
as a director, officer, employee or agent of another corporation or enterprise,
against any liability asserted against him and incurred by him in any such
capacity, or arising out of his status as such, whether or not the corporation
would otherwise have the power to indemnify him under Section 145. The Company
maintains policies insuring its and its subsidiaries' officers and directors
against certain liabilities for actions taken in such capacities, including
liabilities under the Securities Act of 1933, as amended (the "Securities Act").

         The Company's Restated Certificate of Incorporation and Restated Bylaws
require the Company to indemnify the Company's directors to the fullest extent
permitted under Delaware law or any other applicable law in effect, but if such
statute or law is amended, the Company may change the standard of
indemnification only to the extent that such amended statute or law permits the
Company to provide broader indemnification rights to the Company's directors.
Pursuant to employment agreements entered into by the Company with its executive
officers and certain other key employees, the Company must indemnify such
officers and employees in the same manner and to the same extent that the
Company is required to indemnify its directors under its Restated Certificate of
Incorporation and Restated Bylaws. The Company's Restated Certificate of
Incorporation limits the personal liability of a director to the Company or its
stockholders to damages for breach of the director's fiduciary duty.

ITEM 7.  EXEMPTION FROM REGISTRATION CLAIMED.

         The information required by Item 7 is not applicable to this
Registration Statement.

                                      II-2
<PAGE>   4

ITEM 8.  EXHIBITS.

     Exhibit
     Number       Description
     -------      -----------

     3.1(a)+      Restated Certificate of Incorporation (incorporated by
                  reference to Exhibit 3.3 to the Company's Registration
                  Statement on Form SB-2 (No. 33-57728-FW)).

     3.1(b)+      Certificate of Designation of Series One Junior Participating
                  Preferred Stock dated September 2, 1999 (incorporated by
                  reference to Exhibit A to Exhibit 4.1 to the Company's
                  Registration Statement on Form 8-A as filed with the
                  Commission on September 3, 1999).

     3.2+         Restated Bylaws (incorporated by reference to Exhibit 3.4 to
                  the Company's Registration Statement on Form SB-2
                  (No. 33-57728-FW)).

     4.1+         Zonagen, Inc. 2000 Nonemployee Directors' Stock Option Plan
                  (incorporated by reference to Appendix A to the Company's
                  proxy statement filed on April 26, 2000).

     4.2+         First Amendment to the Zonagen, Inc. 2000 Nonemployee
                  Directors' Stock Option Plan (incorporated by reference to
                  Exhibit 10.21 to the Company's annual report on Form 10-K for
                  the fiscal year ended December 31, 2000).

     5.1*         Opinion of Andrews & Kurth L.L.P.

    23.1*         Consent of Andrews & Kurth L.L.P. (included in Exhibit 5.1).

    23.2*         Consent of Arthur Andersen LLP.

    24.1*         Power of Attorney (set forth on the signature page contained
                  in Part II of this Registration Statement).
------------
+ Incorporated herein by reference.
* Filed herewith.

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, represent a fundamental
                  change in the information set forth in this Registration
                  Statement. Notwithstanding the

                                      II-3
<PAGE>   5

                  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 and of the estimated maximum offering range
                  may be reflected in the form of prospectus filed with the
                  Commission pursuant to Rule 424(b) if, in the aggregate, the
                  changes in volume and price represent no more than 20 percent
                  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 this Registration Statement;

         Provided, however, that paragraphs (a)(1)(i) and (a)(1)(ii) above do
         not apply if the information required to be included in a
         post-effective amendment by those paragraphs is contained in periodic
         reports filed by the Company pursuant to Section 13 or Section 15(d) of
         the Securities Exchange Act of 1934 that are incorporated by reference
         in the 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 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
Company's annual report pursuant to Section 13(a) or 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 Company pursuant to the foregoing provisions, or otherwise, the
Company 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 Company of expenses
incurred or paid by a director, officer or controlling person of the Company 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 Company 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>   6

                                   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 Woodlands, Texas, on the 6th day of April, 2001.

                                        ZONAGEN, INC.

                                        By: /s/ Joseph S. Podolski
                                           -------------------------------------
                                           Joseph S. Podolski
                                           President and Chief Executive Officer

                                POWER OF ATTORNEY

         KNOW ALL MEN BY THESE PRESENTS, that each of the undersigned officers
and directors of Zonagen, Inc. (the "Company") hereby constitutes and appoints
Joseph S. Podolski and Louis Ploth, Jr., and each of them (with full power to
each of them to act alone), his true and lawful attorney-in-fact and agent, with
full power of substitution, for him and on his behalf and in his name, place and
stead, in any and all capacities, to sign, execute and file this Registration
Statement under the Securities Act of 1933, as amended, and any or all
amendments (including, without limitation, post-effective amendments), with all
exhibits and any and all documents required to be filed with respect thereto,
with the Securities and Exchange Commission or any regulatory authority,
granting unto such 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 order to effectuate the same, as fully to all intents
and purposes as he himself might or could do if personally present, hereby
ratifying and confirming all that such attorneys-in-fact and agents, or any of
them, or their substitute or substitutes, may lawfully do or cause to be done.

         PURSUANT TO THE REQUIREMENTS OF THE SECURITIES ACT OF 1933, THIS
REGISTRATION STATEMENT HAS BEEN SIGNED BY THE FOLLOWING PERSONS IN THE
CAPACITIES AND ON THE DATES INDICATED.

<TABLE>
<CAPTION>
                 SIGNATURE                                        TITLE                                DATE
<S>                                             <C>                                                 <C>
    /s/ Martin P. Sutter                              Chairman of the Board of Directors            April 6, 2001
    --------------------------------
        Martin P. Sutter

    /s/ Joseph S. Podolski                           President, Chief Executive Officer             April 6, 2001
    --------------------------------                          and Director
        Joseph S. Podolski                             (Principal Executive Officer)

    /s/ Louis Ploth, Jr.                                   Vice President-Finance,                  April 6, 2001
    --------------------------------               Chief Financial Officer and Secretary
        Louis Ploth, Jr.                        (Principal Accounting and Financial Officer)

    /s/ Steven Blasnik                                            Director                          April 6, 2001
    --------------------------------
        Steven Blasnik

    /s/ Timothy McInerney                                         Director                          April 6, 2001
    --------------------------------
        Timothy McInerney

    /s/ Lloyd M. Bentsen                                          Director                          April 6, 2001
    --------------------------------
        Lloyd M. Bentsen
</TABLE>

                                      II-5
<PAGE>   7

                                 EXHIBIT INDEX

     Exhibit
     Number       Description
     -------      -----------

     3.1(a)+      Restated Certificate of Incorporation (incorporated by
                  reference to Exhibit 3.3 to the Company's Registration
                  Statement on Form SB-2 (No. 33-57728-FW)).

     3.1(b)+      Certificate of Designation of Series One Junior Participating
                  Preferred Stock dated September 2, 1999 (incorporated by
                  reference to Exhibit A to Exhibit 4.1 to the Company's
                  Registration Statement on Form 8-A as filed with the
                  Commission on September 3, 1999).

     3.2+         Restated Bylaws (incorporated by reference to Exhibit 3.4 to
                  the Company's Registration Statement on Form SB-2
                  (No. 33-57728-FW)).

     4.1+         Zonagen, Inc. 2000 Nonemployee Directors' Stock Option Plan
                  (incorporated by reference to Appendix A to the Company's
                  proxy statement filed on April 26, 2000).

     4.2+         First Amendment to the Zonagen, Inc. 2000 Nonemployee
                  Directors' Stock Option Plan (incorporated by reference to
                  Exhibit 10.21 to the Company's annual report on Form 10-K for
                  the fiscal year ended December 31, 2000).

     5.1*         Opinion of Andrews & Kurth L.L.P.

    23.1*         Consent of Andrews & Kurth L.L.P. (included in Exhibit 5.1).

    23.2*         Consent of Arthur Andersen LLP.

    24.1*         Power of Attorney (set forth on the signature page contained
                  in Part II of this Registration Statement).
------------
+ Incorporated herein by reference.
* Filed herewith.
[{"type": "S-8", "sequence": "1", "filename": "h85943s-8.txt", "description": "ZONAGEN INC", "secsgml_size_bytes": 21810}]
{"company-data": {"conformed-name": "ZONAGEN INC", "cik": "0000897075", "assigned-sic": "2836", "irs-number": "760233274", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-58542", "film-number": "1598152"}, "business-address": {"street1": "2408 TIMBERLOCH PL", "street2": "SUITE B-4", "city": "WOODLANDS", "state": "TX", "zip": "77380", "phone": "2813675892"}, "mail-address": {"street1": "2408 TIMBERLOCH PLACE B-4", "city": "THE WOODLANDS", "state": "TX", "zip": "77380"}}
1

     AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON APRIL 9, 2001

                                                   REGISTRATION NO. 333-
================================================================================

                       SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549

                                    FORM S-8

                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                                  ZONAGEN, INC.
             (EXACT NAME OF REGISTRANT AS SPECIFIED IN ITS CHARTER)

                  DELAWARE                                   76-0233274
       (STATE OR OTHER JURISDICTION OF                    (I.R.S. EMPLOYER
       INCORPORATION OR ORGANIZATION)                    IDENTIFICATION NO.)

      2408 TIMBERLOCH PLACE, SUITE B-4
            THE WOODLANDS, TEXAS                                77380
   (ADDRES OF PRINCIPAL EXECUTIVE OFFICES)                    (ZIP CODE)

                  2000 NONEMPLOYEE DIRECTORS' STOCK OPTION PLAN
                        2000 EMPLOYEE STOCK PURCHASE PLAN
                            (FULL TITLE OF THE PLANS)

                               JOSEPH S. PODOLSKI
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                        2408 TIMBERLOCH PLACE, SUITE B-4
                           THE WOODLANDS, TEXAS 77380
                     (NAME AND ADDRESS OF AGENT FOR SERVICE)
                                 (281) 719-3400
          (TELEPHONE NUMBER, INCLUDING AREA CODE, OF AGENT FOR SERVICE)

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

                                    COPY TO:
                             JEFFREY R. HARDER, ESQ.
                             ANDREWS & KURTH L.L.P.
                        2170 BUCKTHORNE PLACE, SUITE 150
                           THE WOODLANDS, TEXAS 77380
                                 (713) 220-4801

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

                         CALCULATION OF REGISTRATION FEE
===================================================================================================================

                                                                                    PROPOSED MAXIMUM
                                                  AMOUNT         PROPOSED MAXIMUM       AGGREGATE       AMOUNT OF
                                                  TO BE           OFFERING PRICE     OFFERING PRICE    REGISTRATION
       TITLE OF PLAN TO BE REGISTERED          REGISTERED(1)      PER SHARE (2)            (2)             FEE
===================================================================================================================
2000 Nonemployee Directors' Stock Option
  Plan                                         500,000 shares         $2.81            $1,405,000        $351.25
-------------------------------------------------------------------------------------------------------------------
2000 Employee Stock Purchase Plan              150,000 shares         $2.81             $421,500         $105.38
===================================================================================================================
(1) Pursuant to Rule 416 of the Securities Act, this number includes an
    indeterminate number of additional shares that may be issued under the
    above-referenced plans as a result of anti-dilution provisions, stock
    splits, stock dividends or similar transactions.

(2) Estimated solely for the purpose of calculating the registration fee
    pursuant to Rule 457(c) and (h), based upon the average of the high and low
    sales prices per share of the Registrant's Common Stock reported on The
    Nasdaq National Market on April 3, 2001.

================================================================================
2

                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

ITEM 3.  INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE.

         Zonagen, Inc. (the "Company") incorporates herein by reference the
following documents as of their respective dates as filed with the Securities
and Exchange Commission (the "Commission"):

                  (a) The Company's Annual Report on Form 10-K (File No.
0-21198) for the year ended December 31, 2000;

                  (b) The description of the Company's common stock, par value
$0.001 per share (the "Common Stock"), contained in the Company's Registration
Statement on Form 8-A filed with the Commission on February 2, 1993, as amended
by Amendment No. 1 thereto filed with the Commission on February 12, 1993 and
Amendment No. 2 thereto filed with the Commission on March 25, 1993.

         All documents filed by the Company pursuant to Section 13(a), 13(c), 14
and 15(d) of the Securities Exchange Act of 1934, as amended (the "Exchange
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 deregisters all such securities then remaining unsold
shall be deemed to be incorporated by reference in this Registration Statement
and to be a part hereof from the date of filing such documents.

ITEM 4.  DESCRIPTION OF SECURITIES.

         The information required by Item 4 is not applicable to this
Registration Statement because the class of securities to be offered is
registered under Section 12 of the Exchange Act.

ITEM 5.  INTERESTS OF NAMED EXPERTS AND COUNSEL.

         The information required by Item 5 is not applicable to this
Registration Statement.

ITEM 6.  INDEMNIFICATION OF DIRECTORS AND OFFICERS.

         Section 145 of the Delaware General Corporation Law ("DGCL"), inter
alia, empowers a Delaware corporation to indemnify any person who was or is a
party or is threatened to be made a party to any threatened, pending or
completed action, suit or proceeding (other than an action by or in the right of
the corporation) by reason of the fact that such person is or was a director,
officer, employee or agent of the corporation, or is or was serving at the
request of the corporation as a director, officer, employee or agent of another
corporation or other enterprise, against expenses (including attorneys' fees),
judgments, fines and amounts paid in settlement actually and reasonably incurred
by him in connection with such action, suit or proceeding if he

                                      II-1
3

acted in good faith and in a manner he reasonably believed to be in or not
opposed to the best interests of the corporation, and, with respect to any
criminal action or proceeding, had no reasonable cause to believe his conduct
was unlawful. Similar indemnity is authorized for such persons against expenses
(including attorneys' fees) actually and reasonably incurred in connection with
the defense or settlement of any such threatened, pending or completed action or
suit if such person acted in good faith and in a manner he reasonably believed
to be in or not opposed to the best interests of the corporation, and provided
further that (unless a court of competent jurisdiction otherwise provides) such
person shall not have been adjudged liable to the corporation. Any such
indemnification may be made only as authorized in each specific case upon a
determination by the stockholders or disinterested directors or by independent
legal counsel in a written opinion that indemnification is proper because the
indemnitee has met the applicable standard of conduct.

         Section 145 further authorizes a corporation to purchase and maintain
insurance on behalf of any person who is or was a director, officer, employee or
agent of the corporation, or is or was serving at the request of the corporation
as a director, officer, employee or agent of another corporation or enterprise,
against any liability asserted against him and incurred by him in any such
capacity, or arising out of his status as such, whether or not the corporation
would otherwise have the power to indemnify him under Section 145. The Company
maintains policies insuring its and its subsidiaries' officers and directors
against certain liabilities for actions taken in such capacities, including
liabilities under the Securities Act of 1933, as amended (the "Securities Act").

         The Company's Restated Certificate of Incorporation and Restated Bylaws
require the Company to indemnify the Company's directors to the fullest extent
permitted under Delaware law or any other applicable law in effect, but if such
statute or law is amended, the Company may change the standard of
indemnification only to the extent that such amended statute or law permits the
Company to provide broader indemnification rights to the Company's directors.
Pursuant to employment agreements entered into by the Company with its executive
officers and certain other key employees, the Company must indemnify such
officers and employees in the same manner and to the same extent that the
Company is required to indemnify its directors under its Restated Certificate of
Incorporation and Restated Bylaws. The Company's Restated Certificate of
Incorporation limits the personal liability of a director to the Company or its
stockholders to damages for breach of the director's fiduciary duty.

ITEM 7.  EXEMPTION FROM REGISTRATION CLAIMED.

         The information required by Item 7 is not applicable to this
Registration Statement.

                                      II-2
4

ITEM 8.  EXHIBITS.

     Exhibit
     Number       Description
     -------      -----------

     3.1(a)+      Restated Certificate of Incorporation (incorporated by
                  reference to Exhibit 3.3 to the Company's Registration
                  Statement on Form SB-2 (No. 33-57728-FW)).

     3.1(b)+      Certificate of Designation of Series One Junior Participating
                  Preferred Stock dated September 2, 1999 (incorporated by
                  reference to Exhibit A to Exhibit 4.1 to the Company's
                  Registration Statement on Form 8-A as filed with the
                  Commission on September 3, 1999).

     3.2+         Restated Bylaws (incorporated by reference to Exhibit 3.4 to
                  the Company's Registration Statement on Form SB-2
                  (No. 33-57728-FW)).

     4.1+         Zonagen, Inc. 2000 Nonemployee Directors' Stock Option Plan
                  (incorporated by reference to Appendix A to the Company's
                  proxy statement filed on April 26, 2000).

     4.2+         First Amendment to the Zonagen, Inc. 2000 Nonemployee
                  Directors' Stock Option Plan (incorporated by reference to
                  Exhibit 10.21 to the Company's annual report on Form 10-K for
                  the fiscal year ended December 31, 2000).

     5.1*         Opinion of Andrews & Kurth L.L.P.

    23.1*         Consent of Andrews & Kurth L.L.P. (included in Exhibit 5.1).

    23.2*         Consent of Arthur Andersen LLP.

    24.1*         Power of Attorney (set forth on the signature page contained
                  in Part II of this Registration Statement).
------------
+ Incorporated herein by reference.
* Filed herewith.

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, represent a fundamental
                  change in the information set forth in this Registration
                  Statement. Notwithstanding the

                                      II-3
5

                  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 and of the estimated maximum offering range
                  may be reflected in the form of prospectus filed with the
                  Commission pursuant to Rule 424(b) if, in the aggregate, the
                  changes in volume and price represent no more than 20 percent
                  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 this Registration Statement;

         Provided, however, that paragraphs (a)(1)(i) and (a)(1)(ii) above do
         not apply if the information required to be included in a
         post-effective amendment by those paragraphs is contained in periodic
         reports filed by the Company pursuant to Section 13 or Section 15(d) of
         the Securities Exchange Act of 1934 that are incorporated by reference
         in the 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 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
Company's annual report pursuant to Section 13(a) or 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 Company pursuant to the foregoing provisions, or otherwise, the
Company 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 Company of expenses
incurred or paid by a director, officer or controlling person of the Company 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 Company 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
6

                                   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 Woodlands, Texas, on the 6th day of April, 2001.

                                        ZONAGEN, INC.

                                        By: /s/ Joseph S. Podolski
                                           -------------------------------------
                                           Joseph S. Podolski
                                           President and Chief Executive Officer

                                POWER OF ATTORNEY

         KNOW ALL MEN BY THESE PRESENTS, that each of the undersigned officers
and directors of Zonagen, Inc. (the "Company") hereby constitutes and appoints
Joseph S. Podolski and Louis Ploth, Jr., and each of them (with full power to
each of them to act alone), his true and lawful attorney-in-fact and agent, with
full power of substitution, for him and on his behalf and in his name, place and
stead, in any and all capacities, to sign, execute and file this Registration
Statement under the Securities Act of 1933, as amended, and any or all
amendments (including, without limitation, post-effective amendments), with all
exhibits and any and all documents required to be filed with respect thereto,
with the Securities and Exchange Commission or any regulatory authority,
granting unto such 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 order to effectuate the same, as fully to all intents
and purposes as he himself might or could do if personally present, hereby
ratifying and confirming all that such attorneys-in-fact and agents, or any of
them, or their substitute or substitutes, may lawfully do or cause to be done.

         PURSUANT TO THE REQUIREMENTS OF THE SECURITIES ACT OF 1933, THIS
REGISTRATION STATEMENT HAS BEEN SIGNED BY THE FOLLOWING PERSONS IN THE
CAPACITIES AND ON THE DATES INDICATED.
SIGNATURE                                        TITLE                                DATE
/s/ Martin P. Sutter                              Chairman of the Board of Directors            April 6, 2001
    --------------------------------
        Martin P. Sutter

    /s/ Joseph S. Podolski                           President, Chief Executive Officer             April 6, 2001
    --------------------------------                          and Director
        Joseph S. Podolski                             (Principal Executive Officer)

    /s/ Louis Ploth, Jr.                                   Vice President-Finance,                  April 6, 2001
    --------------------------------               Chief Financial Officer and Secretary
        Louis Ploth, Jr.                        (Principal Accounting and Financial Officer)

    /s/ Steven Blasnik                                            Director                          April 6, 2001
    --------------------------------
        Steven Blasnik

    /s/ Timothy McInerney                                         Director                          April 6, 2001
    --------------------------------
        Timothy McInerney

    /s/ Lloyd M. Bentsen                                          Director                          April 6, 2001
    --------------------------------
        Lloyd M. Bentsen
II-5
7

                                 EXHIBIT INDEX

     Exhibit
     Number       Description
     -------      -----------

     3.1(a)+      Restated Certificate of Incorporation (incorporated by
                  reference to Exhibit 3.3 to the Company's Registration
                  Statement on Form SB-2 (No. 33-57728-FW)).

     3.1(b)+      Certificate of Designation of Series One Junior Participating
                  Preferred Stock dated September 2, 1999 (incorporated by
                  reference to Exhibit A to Exhibit 4.1 to the Company's
                  Registration Statement on Form 8-A as filed with the
                  Commission on September 3, 1999).

     3.2+         Restated Bylaws (incorporated by reference to Exhibit 3.4 to
                  the Company's Registration Statement on Form SB-2
                  (No. 33-57728-FW)).

     4.1+         Zonagen, Inc. 2000 Nonemployee Directors' Stock Option Plan
                  (incorporated by reference to Appendix A to the Company's
                  proxy statement filed on April 26, 2000).

     4.2+         First Amendment to the Zonagen, Inc. 2000 Nonemployee
                  Directors' Stock Option Plan (incorporated by reference to
                  Exhibit 10.21 to the Company's annual report on Form 10-K for
                  the fiscal year ended December 31, 2000).

     5.1*         Opinion of Andrews & Kurth L.L.P.

    23.1*         Consent of Andrews & Kurth L.L.P. (included in Exhibit 5.1).

    23.2*         Consent of Arthur Andersen LLP.

    24.1*         Power of Attorney (set forth on the signature page contained
                  in Part II of this Registration Statement).
------------
+ Incorporated herein by reference.
* Filed herewith.