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<P align="center" style="font-size: 10pt"><B>As filed with the Securities and Exchange Commission on May&nbsp;23, 2005.</B>



<P align="right" style="font-size: 10pt"><B>Registration No.&nbsp;333-</B><U>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</U>



<DIV style="width: 100%; border-bottom: 2pt solid black; font-size: 1pt">&nbsp;</DIV>
<DIV style="width: 100%; border-bottom: 1pt solid black; font-size: 1pt">&nbsp;</DIV>




<P align="center" style="font-size: 14pt"><B>SECURITIES AND EXCHANGE COMMISSION</B>

<DIV align="center" style="font-size: 12pt"><B>Washington, D.C. 20549</B>
</DIV>


<P align="center" style="font-size: 10pt"><HR size="1" noshade width="10%" align="center" color="#000000">


<P align="center" style="font-size: 18pt"><B>FORM S-8</B>

<DIV align="center" style="font-size: 12pt"><B>REGISTRATION STATEMENT<BR>
UNDER<BR>
THE SECURITIES ACT OF 1933</B></DIV>



<P align="center" style="font-size: 10pt"><HR size="1" noshade width="10%" align="center" color="#000000">


<P align="center" style="font-size: 24pt"><B>ENCYSIVE PHARMACEUTICALS INC.</B>


<DIV align="center" style="font-size: 10pt">(Exact Name of Registrant as Specified in Its Charter)</DIV>



<P align="center" style="font-size: 10pt"><HR size="1" noshade width="10%" align="center" color="#000000">


<DIV align="center">
<TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
<!-- Begin Table Head -->
<TR valign="bottom">
    <TD width="47%">&nbsp;</TD>
    <TD width="5%">&nbsp;</TD>
    <TD width="47%">&nbsp;</TD>
</TR>
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<!-- Begin Table Body -->
<TR valign="bottom">
    <TD align="center" valign="top"><B>Delaware</B><BR>
(State or Other Jurisdiction<BR>
of Incorporation or Organization)
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top"><B>13-3532643</B><BR>
(I.R.S. Employer<BR>
Identification No.)</TD>
</TR>
<!-- End Table Body -->
</TABLE>
</DIV>


<P align="center" style="font-size: 10pt"><B>4848 Loop Central Drive, Suite&nbsp;700<BR>
Houston, Texas 77081</B><BR>
(Address and Zip Code of Principal Executive Offices)



<P align="center" style="font-size: 10pt"><HR size="1" noshade width="10%" align="center" color="#000000">



<P align="center" style="font-size: 10pt"><B>ENCYSIVE PHARMACEUTICALS INC.<BR>
AMENDED AND RESTATED 1999 STOCK INCENTIVE PLAN</B>



<P align="center" style="font-size: 10pt">(Full Title of the Plan)



<P align="center" style="font-size: 10pt"><HR size="1" noshade width="10%" align="center" color="#000000">


<DIV align="center">
<TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
<!-- Begin Table Head -->
<TR valign="bottom">
    <TD width="47%">&nbsp;</TD>
    <TD width="5%">&nbsp;</TD>
    <TD width="47%">&nbsp;</TD>
</TR>
<!-- End Table Head -->
<!-- Begin Table Body -->
<TR valign="bottom">
    <TD align="center" valign="top">Name, Address and Telephone
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">Copy of Communications to:</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">Number of Agent for Service:</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top"><B>Stephen L. Mueller</B></TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top"><B>Vice President, Finance and Administration, Secretary</B></TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top"><B>and Treasurer</B>
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top"><B>Robert G. Reedy</B></TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top"><B>Encysive Pharmaceuticals Inc.</B>
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top"><B>Porter &#038; Hedges, L.L.P.</B></TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top"><B>4848 Loop Central Drive, Suite&nbsp;700</B>
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top"><B>1000 Main Street, 36<SUP style="font-size: 85%; vertical-align: text-top">th</SUP> Floor</B></TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top"><B>Houston, Texas 77081</B>
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top"><B>Houston, Texas 77002-6336</B></TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top"><B>(713)&nbsp;796-8822</B>
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top"><B>(713)&nbsp;226-6000</B></TD>
</TR>
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</TABLE>
</DIV>


<P align="center" style="font-size: 10pt"><B>CALCULATION OF REGISTRATION FEE</B>


<DIV align="center">
<TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
<!-- Begin Table Head -->
<TR valign="bottom">
    <TD width="1%">&nbsp;</TD>
    <TD width="46%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD><!-- VRule -->
    <TD width="1%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD>
    <TD width="7%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD><!-- VRule -->
    <TD width="1%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD>
    <TD width="7%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD><!-- VRule -->
    <TD width="1%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD>
    <TD width="7%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD><!-- VRule -->
    <TD width="1%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD>
    <TD width="7%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD>

    <TD width="1%">&nbsp;</TD>
</TR><TR style="font-size: 1px" valign="bottom">
    <TD nowrap align="left" colspan="23" style="border-bottom: 3px solid #000000">&nbsp;</TD>
</TR>
<TR style="font-size: 8pt" valign="bottom">    <TD width="1%">&nbsp;</TD>

    <TD>&nbsp;</TD>
    <TD style="border-right: 2px solid #000000">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD style="border-right: 2px solid #000000">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD style="border-right: 2px solid #000000">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center" colspan="2"><B>Proposed</B></TD>
    <TD>&nbsp;</TD>
    <TD style="border-right: 2px solid #000000">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center" colspan="2">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD width="1%">&nbsp;</TD>
</TR>
<TR style="font-size: 8pt" valign="bottom">    <TD width="1%">&nbsp;</TD>

    <TD>&nbsp;</TD>
    <TD style="border-right: 2px solid #000000">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center" colspan="2"><B>Amount to</B></TD>
    <TD>&nbsp;</TD>
    <TD style="border-right: 2px solid #000000">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center" colspan="2"><B>Proposed Maximum Offering</B></TD>
    <TD>&nbsp;</TD>
    <TD style="border-right: 2px solid #000000">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center" colspan="2"><B>Maximum Aggregate</B></TD>
    <TD>&nbsp;</TD>
    <TD style="border-right: 2px solid #000000">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center" colspan="2"><B>Amount of</B></TD>
    <TD>&nbsp;</TD>
    <TD width="1%">&nbsp;</TD>
</TR>
<TR style="font-size: 8pt" valign="bottom">    <TD width="1%">&nbsp;</TD>

    <TD nowrap align="left"><B>Title of Each Class of Securities to be Registered</B></TD>
    <TD style="border-right: 2px solid #000000">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center" colspan="2"><B>be Registered (1)</B></TD>
    <TD>&nbsp;</TD>
    <TD style="border-right: 2px solid #000000">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center" colspan="2"><B>Price per Share (2)</B></TD>
    <TD>&nbsp;</TD>
    <TD style="border-right: 2px solid #000000">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center" colspan="2"><B>Offering Price (2)</B></TD>
    <TD>&nbsp;</TD>
    <TD style="border-right: 2px solid #000000">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center" colspan="2"><B>Registration Fee</B></TD>
    <TD>&nbsp;</TD>
    <TD width="1%">&nbsp;</TD>
</TR>

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<TR valign="bottom">
    <TD width="1%" style="border-top: 2px solid #000000">&nbsp;</TD>
                    <TD style="border-top: 2px solid #000000"><DIV style="margin-left:15px; text-indent:-15px">Common Stock, par value $.005 per share</DIV></TD>
    <TD style="border-right: 2px solid #000000; border-top: 2px solid #000000">&nbsp;</TD>
    <TD style="border-top: 2px solid #000000">&nbsp;</TD>
    <TD nowrap align="left" style="border-top: 2px solid #000000">&nbsp;</TD>
    <TD align="right" style="border-top: 2px solid #000000">2,000,000</TD>
    <TD nowrap style="border-top: 2px solid #000000">(3)</TD>
    <TD style="border-right: 2px solid #000000; border-top: 2px solid #000000">&nbsp;</TD>
    <TD style="border-top: 2px solid #000000">&nbsp;</TD>
    <TD align="left" style="border-top: 2px solid #000000">&nbsp;</TD>
    <TD align="center" style="border-top: 2px solid #000000">$10.05</TD>
    <TD style="border-top: 2px solid #000000">&nbsp;</TD>
    <TD style="border-right: 2px solid #000000; border-top: 2px solid #000000">&nbsp;</TD>
    <TD style="border-top: 2px solid #000000">&nbsp;</TD>
    <TD align="left" style="border-top: 2px solid #000000">&nbsp;</TD>
    <TD align="center" style="border-top: 2px solid #000000">$20,100,000</TD>
    <TD style="border-top: 2px solid #000000">&nbsp;</TD>
    <TD style="border-right: 2px solid #000000; border-top: 2px solid #000000">&nbsp;</TD>
    <TD style="border-top: 2px solid #000000">&nbsp;</TD>
    <TD align="left" style="border-top: 2px solid #000000">&nbsp;</TD>
    <TD align="center" style="border-top: 2px solid #000000">$2,366</TD>
    <TD style="border-top: 2px solid #000000">&nbsp;</TD>
    <TD width="1%" style="border-top: 2px solid #000000">&nbsp;</TD>
</TR>
<TR style="font-size: 1px" valign="bottom">
    <TD nowrap align="left" colspan="23" style="border-top: 3px solid #000000">&nbsp;</TD>
</TR>

<!-- End Table Body -->
</TABLE>
</DIV>

<P>
<TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">

<TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
    <TD width="1%" nowrap align="left">(1)&nbsp;&nbsp;</TD>
    <TD>Pursuant to Rule&nbsp;416(a), also registered hereunder are an indeterminate number of shares
of common stock issuable as a result of the anti-dilution provisions of the Encysive
Pharmaceuticals Inc. Amended and Restated 1999 Stock Incentive Plan (the &#147;Plan&#148;).</TD>
</TR>

<TR>
    <TD colspan="5">&nbsp;</TD>
</TR>
<TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
    <TD width="1%" nowrap align="left">(2)&nbsp;&nbsp;</TD>
    <TD>Pursuant to Rule&nbsp;457(c), the registration fee is calculated on the basis of the average of
the high and low sale prices for the common stock on The Nasdaq Stock Market on May&nbsp;18, 2005,
$10.05. Pursuant to General Instruction E to Form S-8, the registration fee is calculated
only with respect to additional securities registered under the Plan.</TD>
</TR>

<TR>
    <TD colspan="5">&nbsp;</TD>
</TR>
<TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
    <TD width="1%" nowrap align="left">(3)&nbsp;&nbsp;</TD>
    <TD>Includes one preferred stock purchase right (the &#147;Rights&#148;) for each share of common stock.
Pursuant to Rule 457(g) of the Securities Act no separate fee is required for the Rights.</TD>
</TR>

</TABLE>


<DIV style="width: 100%; border-bottom: 1pt solid black; margin-top: 10pt; font-size: 1pt">&nbsp;</DIV>
<DIV style="width: 100%; border-bottom: 2pt solid black; font-size: 1pt">&nbsp;</DIV>





<P align="center" style="font-size: 10pt">&nbsp;</DIV>

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<H5 align="left" style="page-break-before:always">&nbsp;</H5><P>

<DIV style="font-family: 'Times New Roman',Times,serif">

<P align="center" style="font-size: 10pt"><B>Statement Under General Instruction E &#151; Registration of Additional Securities</B>



<P align="left" style="font-size: 10pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;This registration statement registers an additional 2,000,000 shares of our common stock
related to the Amended and Restated 1999 Stock Incentive Plan which are the same class as other
securities for which registration statements on Form S-8, File No.&nbsp;333-116178, File No.&nbsp;333-107941,
File No.&nbsp;333-72468 and File No.&nbsp;333-79477 (the &#147;Prior Registration Statements&#148;), have been
previously filed. Pursuant to General Instruction E of Form S-8, the contents of the Prior
Registration Statements are hereby incorporated by reference.

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<P align="left" style="font-size: 10pt"><B>Item&nbsp;8. Exhibits</B>


<DIV align="center">
<TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
<!-- Begin Table Head -->
<TR valign="bottom">
    <TD width="3%">&nbsp;</TD>
    <TD width="7%">&nbsp;</TD>
    <TD width="90%">&nbsp;</TD>
</TR>
<TR style="font-size: 8pt" valign="bottom">
    <TD nowrap align="center"><B>Exhibit</B></TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center">&nbsp;</TD>
</TR>
<TR style="font-size: 8pt" valign="bottom">
    <TD nowrap align="center" style="border-bottom: 1px solid #000000"><B>No.</B></TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center" style="border-bottom: 1px solid #000000"><B>Description</B></TD>
</TR>

<!-- End Table Head -->
<!-- Begin Table Body -->
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">4.1
</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Encysive Pharmaceuticals Inc. Amended and Restated 1999 Stock Incentive Plan
(incorporated herein by reference to Appendix&nbsp;B of the Proxy Statement on
Schedule&nbsp;14A filed April&nbsp;7, 2005).</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">*5.1
</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Opinion of Porter &#038; Hedges, L.L.P. with respect to the legality of the securities.</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">*23.1
</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Consent of Porter &#038; Hedges, L.L.P. (included in Exhibit&nbsp;5.1).</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">*23.2
</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Consent of KPMG LLP.</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">*24.1
</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Power of Attorney (included on signature page of this registration statement).</TD>
</TR>
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</TABLE>
</DIV>



<P>
<HR size="1" width="18%" align="left" noshade color="#000000">

<TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">

<TR valign="top">
    <TD width="1%" nowrap align="left">*</TD>
    <TD width="3%">&nbsp;</TD>
    <TD width="96%">Filed herewith.</TD>
</TR>

</TABLE>



<P align="center" style="font-size: 10pt">2</DIV>

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<H5 align="left" style="page-break-before:always">&nbsp;</H5><P>

<DIV style="font-family: 'Times New Roman',Times,serif">
<!-- link1 "SIGNATURES" -->

<P align="center" style="font-size: 10pt"><B>SIGNATURES</B>



<P align="left" style="font-size: 10pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;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 Houston, state of Texas, on this 23rd day of May, 2005.


<TABLE width="100%" border="0" cellspacing="0" cellpadding="0" style="font-size: 10pt">
<TR>
    <TD width="48%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD>
    <TD width="1%">&nbsp;</TD>
    <TD width="35%">&nbsp;</TD>
    <TD width="15%">&nbsp;</TD>
</TR>
<TR>
    <TD valign="top" align="left">&nbsp;</TD>
    <TD colspan="3" align="left"><B>ENCYSIVE PHARMACEUTICALS INC.</B><BR>
&nbsp;</TD>
    <TD>&nbsp;</TD>
</TR><TR>
    <TD align="left">&nbsp;</TD>
    <TD valign="top">By:&nbsp;&nbsp;</TD>
    <TD colspan="2" style="border-bottom: 1px solid #000000" align="left">/s/ Bruce D. Given, M.D.
&nbsp;</TD>
    <TD>&nbsp;</TD>
</TR><TR>
    <TD align="left">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD colspan="2" align="left">Bruce D. Given, M.D.&nbsp;</TD>
    <TD>&nbsp;</TD>
</TR><TR>
    <TD align="left">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD colspan="2" align="left">President and Chief Executive Officer&nbsp;</TD>
    <TD>&nbsp;</TD>
</TR>
<TR>
    <TD colspan="5">&nbsp;</TD>
</TR>
</TABLE>

<P align="center" style="font-size: 10pt"><B>POWER OF ATTORNEY</B>




<P align="left" style="font-size: 10pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;KNOW ALL MEN BY THESE PRESENTS, that each person whose signature appears below constitutes and
appoints Bruce D. Given, M.D. and Stephen L. Mueller, and each of them, either of whom may act
without joinder of the other, his or her true and lawful attorneys-in-fact and agents, with full
power of substitution and resubstitution, for him or her and in his or her name, place and stead,
in any and all capacities, to sign any or all pre- and post-effective amendments and supplements to
this registration statement, and to file the same, or cause to be filed the same, with all exhibits
thereto, and other documents in connection therewith, with the Securities and Exchange Commission,
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 and about the
premises, as fully to all intents and purposes as he or she might or could do in person, hereby
ratifying and confirming all that said attorneys-in-fact and agents, and each of them, or the
substitute or substitutes of either of them, may lawfully do or cause to be done by virtue hereof.


<P align="left" style="font-size: 10pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Pursuant to the provisions of the Securities Act of 1933, this registration statement has been
signed by the following persons in the capacities and on the date indicated.

<DIV align="center">
<TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
<!-- Begin Table Head -->
<TR valign="bottom">
    <TD width="31%">&nbsp;</TD>
    <TD width="13%">&nbsp;</TD>
    <TD width="31%">&nbsp;</TD>
    <TD width="3%">&nbsp;</TD>
    <TD width="21%">&nbsp;</TD>
</TR>
<TR style="font-size: 8pt" valign="bottom">
    <TD nowrap align="center"><U><B>Signature</B></U></TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center"><U><B>Title</B></U></TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center"><U><B>Date</B></U></TD>
</TR>

<!-- End Table Head -->
<!-- Begin Table Body -->
<TR valign="bottom">
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">/s/ John M. Pietruski<BR>
<HR size="1" noshade color="#000000">
John M. Pietruski
</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Chairman of the Board of Directors&nbsp;
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">May&nbsp;23, 2005&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">/s/ Bruce D. Given<BR>
<HR size="1" noshade color="#000000">
Bruce D. Given, M.D.
</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">President, Chief Executive&nbsp;Officer <BR>
and Director (Principal<BR>
Executive Officer)
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">May&nbsp;23, 2005&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">/s/ Richard A. F. Dixon<BR>
<HR size="1" noshade color="#000000">
Richard A. F. Dixon, Ph.D.
</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Senior Vice President, Research,&nbsp;Chief <BR>
Scientific Officer and<BR>
Director
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">May&nbsp;23, 2005&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">/s/ Stephen L. Mueller<BR>
<HR size="1" noshade color="#000000">
Stephen L. Mueller
</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Vice President, Finance and&nbsp;Administration, <BR>
Secretary and<BR>
Treasurer (Principal Financial<BR>
and Accounting Officer)
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">May&nbsp;23, 2005&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">/s/ James T. Willerson<BR>
<HR size="1" noshade color="#000000">
James T. Willerson, M.D.
</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Chairman of the Scientific&nbsp;Advisory <BR>
Board and Director
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">May&nbsp;23, 2005&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">/s/ Ron J. Anderson<BR>
<HR size="1" noshade color="#000000">
Ron J. Anderson, M.D.
</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Director&nbsp;
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">May&nbsp;23, 2005&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">/s/ J. Kevin Buchi<BR>
<HR size="1" noshade color="#000000">
J. Kevin Buchi
</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Director&nbsp;
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">May&nbsp;23, 2005&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">/s/ Frank C. Carlucci<BR>
<HR size="1" noshade color="#000000">
Frank C. Carlucci
</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Director&nbsp;
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">May&nbsp;23, 2005&nbsp;</TD>
</TR>
<!-- End Table Body -->
</TABLE>
</DIV>


<P align="center" style="font-size: 10pt">3</DIV>

<!-- PAGEBREAK -->
<P><HR noshade><P>
<H5 align="left" style="page-break-before:always">&nbsp;</H5><P>

<DIV style="font-family: 'Times New Roman',Times,serif">
<DIV align="center">
<TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
<!-- Begin Table Head -->
<TR valign="bottom">
    <TD width="31%">&nbsp;</TD>
    <TD width="13%">&nbsp;</TD>
    <TD width="31%">&nbsp;</TD>
    <TD width="3%">&nbsp;</TD>
    <TD width="21%">&nbsp;</TD>
</TR>
<TR style="font-size: 8pt" valign="bottom">
    <TD nowrap align="center"><U><B>Signature</B></U></TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="left">&nbsp;&nbsp;&nbsp;&nbsp;<U><B>Title</B></U></TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center"><U><B>Date</B></U></TD>
</TR>

<!-- End Table Head -->
<!-- Begin Table Body -->
<TR valign="bottom">
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">/s/ Robert J. Cruikshank<BR>
<HR size="1" noshade color="#000000">
Robert J. Cruikshank
</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Director&nbsp;
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">May&nbsp;23, 2005&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">/s/ John H. Dillon<BR>
<HR size="1" noshade color="#000000">
John H. Dillon, II
</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Director&nbsp;
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">May&nbsp;23, 2005&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">/s/ Suzanne Oparil<BR>
<HR size="1" noshade color="#000000">
Suzanne Oparil, M.D.
</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Director&nbsp;
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">May&nbsp;23, 2005&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD align="center" valign="top">/s/ James A. Thomson<BR>
<HR size="1" noshade color="#000000">
James A. Thomson, Ph.D.
</TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Director&nbsp;
</TD>
    <TD>&nbsp;</TD>
    <TD align="center" valign="top">May&nbsp;23, 2005&nbsp;</TD>
</TR>
<!-- End Table Body -->
</TABLE>
</DIV>


<P align="center" style="font-size: 10pt">4</DIV>

<!-- PAGEBREAK -->
<P><HR noshade><P>
<H5 align="left" style="page-break-before:always">&nbsp;</H5><P>

<DIV style="font-family: 'Times New Roman',Times,serif">
<!-- link1 "INDEX TO EXHIBITS" -->

<P align="center" style="font-size: 10pt"><B>INDEX TO EXHIBITS</B>


<DIV align="center">
<TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
<!-- Begin Table Head -->
<TR valign="bottom">
    <TD width="3%">&nbsp;</TD>
    <TD width="7%">&nbsp;</TD>
    <TD width="90%">&nbsp;</TD>
</TR>
<TR style="font-size: 8pt" valign="bottom">
    <TD nowrap align="center"><B>Exhibit</B></TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center">&nbsp;</TD>
</TR>
<TR style="font-size: 8pt" valign="bottom">
    <TD nowrap align="center" style="border-bottom: 1px solid #000000"><B>No.</B></TD>
    <TD>&nbsp;</TD>
    <TD nowrap align="center" style="border-bottom: 1px solid #000000"><B>Description</B></TD>
</TR>

<!-- End Table Head -->
<!-- Begin Table Body -->
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">4.1
</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Encysive Pharmaceuticals Inc. Amended and Restated 1999 Stock Incentive Plan
(incorporated herein by reference to Appendix&nbsp;B of the Proxy Statement on
Schedule&nbsp;14A filed April&nbsp;7, 2005).</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">*5.1
</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Opinion of Porter &#038; Hedges, L.L.P. with respect to the legality of the securities.</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">*23.1
</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Consent of Porter &#038; Hedges, L.L.P. (included in Exhibit&nbsp;5.1).</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">*23.2
</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Consent of KPMG LLP.</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">&nbsp;</TD>
</TR>
<TR valign="bottom">
    <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">*24.1
</DIV></TD>
    <TD>&nbsp;</TD>
    <TD align="left" valign="top">Power of Attorney (included on signature page of this registration statement).</TD>
</TR>
<!-- End Table Body -->
</TABLE>
</DIV>



<P>
<HR size="1" width="18%" align="left" noshade color="#000000">

<TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">

<TR valign="top">
    <TD width="1%" nowrap align="left">*</TD>
    <TD width="3%">&nbsp;</TD>
    <TD width="96%">Filed herewith.</TD>
</TR>

</TABLE>



<P align="center" style="font-size: 10pt">5</DIV>

</BODY>
</HTML>
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sv8
As filed with the Securities and Exchange Commission on May 23, 2005.
Registration No. 333-
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM S-8
REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933
ENCYSIVE PHARMACEUTICALS INC.
(Exact Name of Registrant as Specified in Its Charter)
Delaware
(State or Other Jurisdiction
of Incorporation or Organization)
13-3532643
(I.R.S. Employer
Identification No.)
4848 Loop Central Drive, Suite 700
Houston, Texas 77081
(Address and Zip Code of Principal Executive Offices)
ENCYSIVE PHARMACEUTICALS INC.
AMENDED AND RESTATED 1999 STOCK INCENTIVE PLAN
(Full Title of the Plan)
Name, Address and Telephone
Copy of Communications to:
Number of Agent for Service:
Stephen L. Mueller
Vice President, Finance and Administration, Secretary
and Treasurer
Robert G. Reedy
Encysive Pharmaceuticals Inc.
Porter & Hedges, L.L.P.
4848 Loop Central Drive, Suite 700
1000 Main Street, 36
th
Floor
Houston, Texas 77081
Houston, Texas 77002-6336
(713) 796-8822
(713) 226-6000
CALCULATION OF REGISTRATION FEE
Proposed
Amount to
Proposed Maximum Offering
Maximum Aggregate
Amount of
Title of Each Class of Securities to be Registered
be Registered (1)
Price per Share (2)
Offering Price (2)
Registration Fee
Common Stock, par value $.005 per share
2,000,000
(3)
$10.05
$20,100,000
$2,366
(1)
Pursuant to Rule 416(a), also registered hereunder are an indeterminate number of shares
of common stock issuable as a result of the anti-dilution provisions of the Encysive
Pharmaceuticals Inc. Amended and Restated 1999 Stock Incentive Plan (the "Plan").
(2)
Pursuant to Rule 457(c), the registration fee is calculated on the basis of the average of
the high and low sale prices for the common stock on The Nasdaq Stock Market on May 18, 2005,
$10.05. Pursuant to General Instruction E to Form S-8, the registration fee is calculated
only with respect to additional securities registered under the Plan.
(3)
Includes one preferred stock purchase right (the "Rights") for each share of common stock.
Pursuant to Rule 457(g) of the Securities Act no separate fee is required for the Rights.
Statement Under General Instruction E — Registration of Additional Securities
This registration statement registers an additional 2,000,000 shares of our common stock
related to the Amended and Restated 1999 Stock Incentive Plan which are the same class as other
securities for which registration statements on Form S-8, File No. 333-116178, File No. 333-107941,
File No. 333-72468 and File No. 333-79477 (the "Prior Registration Statements"), have been
previously filed. Pursuant to General Instruction E of Form S-8, the contents of the Prior
Registration Statements are hereby incorporated by reference.
Item 8. Exhibits
Exhibit
No.
Description
4.1
Encysive Pharmaceuticals Inc. Amended and Restated 1999 Stock Incentive Plan
(incorporated herein by reference to Appendix B of the Proxy Statement on
Schedule 14A filed April 7, 2005).
*5.1
Opinion of Porter & Hedges, L.L.P. with respect to the legality of the securities.
*23.1
Consent of Porter & Hedges, L.L.P. (included in Exhibit 5.1).
*23.2
Consent of KPMG LLP.
*24.1
Power of Attorney (included on signature page of this registration statement).
*
Filed herewith.
2
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 Houston, state of Texas, on this 23rd day of May, 2005.
ENCYSIVE PHARMACEUTICALS INC.
By:
/s/ Bruce D. Given, M.D.
Bruce D. Given, M.D.
President and Chief Executive Officer
POWER OF ATTORNEY
KNOW ALL MEN BY THESE PRESENTS, that each person whose signature appears below constitutes and
appoints Bruce D. Given, M.D. and Stephen L. Mueller, and each of them, either of whom may act
without joinder of the other, his or her true and lawful attorneys-in-fact and agents, with full
power of substitution and resubstitution, for him or her and in his or her name, place and stead,
in any and all capacities, to sign any or all pre- and post-effective amendments and supplements to
this registration statement, and to file the same, or cause to be filed the same, with all exhibits
thereto, and other documents in connection therewith, with the Securities and Exchange Commission,
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 and about the
premises, as fully to all intents and purposes as he or she might or could do in person, hereby
ratifying and confirming all that said attorneys-in-fact and agents, and each of them, or the
substitute or substitutes of either of them, may lawfully do or cause to be done by virtue hereof.
Pursuant to the provisions of the Securities Act of 1933, this registration statement has been
signed by the following persons in the capacities and on the date indicated.
Signature
Title
Date
/s/ John M. Pietruski
John M. Pietruski
Chairman of the Board of Directors
May 23, 2005
/s/ Bruce D. Given
Bruce D. Given, M.D.
President, Chief Executive Officer
and Director (Principal
Executive Officer)
May 23, 2005
/s/ Richard A. F. Dixon
Richard A. F. Dixon, Ph.D.
Senior Vice President, Research, Chief
Scientific Officer and
Director
May 23, 2005
/s/ Stephen L. Mueller
Stephen L. Mueller
Vice President, Finance and Administration,
Secretary and
Treasurer (Principal Financial
and Accounting Officer)
May 23, 2005
/s/ James T. Willerson
James T. Willerson, M.D.
Chairman of the Scientific Advisory
Board and Director
May 23, 2005
/s/ Ron J. Anderson
Ron J. Anderson, M.D.
Director
May 23, 2005
/s/ J. Kevin Buchi
J. Kevin Buchi
Director
May 23, 2005
/s/ Frank C. Carlucci
Frank C. Carlucci
Director
May 23, 2005
3
Signature
Title
Date
/s/ Robert J. Cruikshank
Robert J. Cruikshank
Director
May 23, 2005
/s/ John H. Dillon
John H. Dillon, II
Director
May 23, 2005
/s/ Suzanne Oparil
Suzanne Oparil, M.D.
Director
May 23, 2005
/s/ James A. Thomson
James A. Thomson, Ph.D.
Director
May 23, 2005
4
INDEX TO EXHIBITS
Exhibit
No.
Description
4.1
Encysive Pharmaceuticals Inc. Amended and Restated 1999 Stock Incentive Plan
(incorporated herein by reference to Appendix B of the Proxy Statement on
Schedule 14A filed April 7, 2005).
*5.1
Opinion of Porter & Hedges, L.L.P. with respect to the legality of the securities.
*23.1
Consent of Porter & Hedges, L.L.P. (included in Exhibit 5.1).
*23.2
Consent of KPMG LLP.
*24.1
Power of Attorney (included on signature page of this registration statement).
*
Filed herewith.
5