I have experienced this issue as well. For me, it is caused by the specific combination of all of the following:
- ASP.NET 4.0
- IIS 6.0
- Wildcard Mapping (In the Application Configuration section, add a wildcard mapping to "c:\windows\microsoft.net\framework\v4.0.30319\aspnet_isapi.dll", verify that file exists must be unchecked)
- RadAjaxPanel (2011.1.315.40)
- RadCompression (2011.1.315.40)
- Browsing to default documents with extensionless URLs (http://mysite.com instead of http://mysite.com/default.aspx)
If I change any one of those things (3 through 6), the error goes away. I can remove the wildcard mapping, remove the ajax panel, remove radcompression, or browse to the full filename and everything works fine. However, that is just a work-around.
One other work-around is to add the following to your code-behind (page load, page init, etc):
Page.Form.Action = System.IO.Path.GetFileName(Request.PhysicalPath);
This forces "default.aspx" into the action parameter of the form tag, which also fixes the issue. Without this code, the action is set to empty string, which also contributes to the problem.