I got a complicated problem with ASP.Net 4.0 Ajax....I started a website with Visual Studio 2010 on my machine,and added some update panels they used to work fine,but sudden
Here is the answer by zhughes from this thread on asp.net forum.
The Reason : the path of the javascript generated by the scriptmanager changes when the URL Routing module is used.
The Solution : Tell the routing API to not route the files with "axd" extension (the files generated by the scriptmanager)
Add this rule to the method where you register the routing rules in Global.asax
routes.Ignore("{resource}.axd/{*pathInfo}");
in addition you should have this section in web.config