Another possibility is that the application mappings are not configured correctly (try with “aspnet_regiis –i”) or for some reason for the extension .axd the flag “Verify that file exists” flag has been set: if it is, remove it.
Pay attention to the last entry:
What is important here is the “Flags” part: “4” means “The server attempts to access the PATH_INFO portion of the URL, as a file, before starting the scripting engine. If the file can’t be opened, or doesn’t exist, an error is returned to the client”.
Here we are again… Check and clear the flag “Verify that file exists” for your wildcard application mapping. The point is that a wildcard ISAPI extension intercepts all requests and is executed as the first step for every of them; since WebResource.axd does not exist as a file on disk, IIS will not find it, will return a 404 error and will abort the request without passing it to aspnet_isapi.dll for further handling.