Our project works fine with .Net 3.5 with Telerik 2009.2.701.35 version. When it is migrated to .Net 4.5 framework. It throws error like this. "0x800a139e - Microsoft JScript runtime error: Sys.WebForms.PageRequestManagerServerErrorException: Object reference not set to an instance of an object." Detailed Error message is given. Unhandled exception at line 3, column 69963 in http://localhost:57537/...../Telerik.Web.UI.WebResource.axd?_TSM_HiddenField_=ctl00_DefaultMasterScriptManager_TSM&compress=1&_TSM_CombinedScripts_=; ;AjaxControlToolkit,+Version=4.5.7.725,+Culture=neutral,+PublicKeyToken=28f01b0e84b6d53e:en-US:f3ec7948-9e31-4562-b526-b0088d3f7327: ea597d4b:b25378d2;Telerik.Web.UI,+Version=2013.1.417.45,+Culture=neutral,+PublicKeyToken=121fae78165ba3d4: en-US:42f3bd03-686e-4514-94d4-9dc03944a160:16e4e7cd:ed16cbdc:f7645509:24ee1bba:19620875:874f8ea2:f46195d3:490a9d4e:bd8f85e4: 2003d0b8:e330518b:1e771326:c8618e41:b7778d6c:e085fe68:8e6f0d33:6a6d718d:8674cba1:7c926187:c08e9f8a:a51ee93e:59462f1: aa288e2d:82923ac3:58366029 0x800a139e - Microsoft JScript runtime error: Sys.WebForms.PageRequestManagerServerErrorException: Object reference not set to an instance of an object. If there is a handler for this exception, the program may be safely continued. So it is upgraded to Telerik 2013.1.417.45 version. It is throwing same error. [Even tried with Latest Telerik AspnetAjax Q2 version is also throwing the same error] I suspect that the error might be because the AjaxRadManager and/or skins which is implemented from Telerik.Web.UI. Skins.dll is causing the trouble.