You need to register your Http Handler in the web.config
.
This is configuration of IIS earlier than 7.0
<configuration>
...
<system.web>
...
<httpHandlers>
<remove verb="*" path="*.asmx"/>
<add verb="*" path="*.asmx" validate="false" type="System.Web.Script.Services.ScriptHandlerFactory, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35"/>
<add verb="*" path="*_AppService.axd" validate="false" type="System.Web.Script.Services.ScriptHandlerFactory, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35"/>
<add verb="GET,HEAD" path="ScriptResource.axd" type="System.Web.Handlers.ScriptResourceHandler, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35" validate="false"/>
<add verb="POST" path="SagePay.ashx" type="<Your Handler Namespace>.SagePayHandler, <Your Handler Assembly>" validate="false"/>
</httpHandlers>
<httpModules>
<add name="ScriptModule" type="System.Web.Handlers.ScriptModule, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35"/>
</httpModules>
</system.web>
...
</configuration>
And this is configuration for IIS 7.0:
<configuration>
...
<system.webServer>
...
<handlers>
<remove name="WebServiceHandlerFactory-Integrated"/>
<remove name="ScriptHandlerFactory"/>
<remove name="ScriptHandlerFactoryAppServices"/>
<remove name="ScriptResource"/>
<add name="ScriptHandlerFactory" verb="*" path="*.asmx" preCondition="integratedMode" type="System.Web.Script.Services.ScriptHandlerFactory, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35"/>
<add name="ScriptHandlerFactoryAppServices" verb="*" path="*_AppService.axd" preCondition="integratedMode" type="System.Web.Script.Services.ScriptHandlerFactory, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35"/>
<add name="ScriptResource" verb="GET,HEAD" path="ScriptResource.axd" preCondition="integratedMode" type="System.Web.Handlers.ScriptResourceHandler, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35"/>
<add name="SagePayHandler" verb="POST" path="SagePay.ashx" type="<Your Handler Namespace>.SagePayHandler, <Your Handler Assembly>"/>
</handlers>
<modules>
<remove name="ScriptModule"/>
<add name="ScriptModule" preCondition="managedHandler" type="System.Web.Handlers.ScriptModule, System.Web.Extensions, Version=3.5.0.0, Culture=neutral, PublicKeyToken=31BF3856AD364E35"/>
</modules>
</system.webServer>
...
</configuration>
Of course the important part are the lines refering to your Http Handler.
After this registration your handler will be availble under following URL:
http:\\your.website.com\SagePay.ashx
You can read more about registering HTTP Handlers in following article: How to: Register HTTP Handlers