Sys.WebForms.PageRequestManagerServerErrorException: An unknown error occurred while processing the request on the server."

This issue sometimes occurs when you have a control registered as an AsyncPostbackTrigger in multiple update panels.

If that's not the problem, try adding the following right after the script manager declaration, which I found in this post by manowar83, which copies and slightly modifies this post by larryw:

<script type="text/javascript" language="javascript">
    Sys.WebForms.PageRequestManager.getInstance().add_endRequest(EndRequestHandler);
    function EndRequestHandler(sender, args){
        if (args.get_error() != undefined){
            args.set_errorHandled(true);
        }
    }
</script>

There are a few more solutions discussed here: http://forums.asp.net/t/1066976.aspx/9/10

I had this issue and I spent hours trying to fix it.

The solution ticked as answered will not fix the error only handle it.

The best approach is to check the IIS log files and the error should be there. It appears that the update panel encapsulates the real error and outputs it as a 'javascript error'.

For instance my error was that I forgot to make a class [Serializable]. Although this worked fine locally it did not work when deployed on the server.

I got this error when I had my button in the GridView in an UpdatePanel... deubbing my code I found that the above error is caused because of another internal error "A potentially dangerous Request.Form value was detected from the client"

Finally I figured out that one of my TextBoxes on the page has XML/HTML content and this in-turn causing above error when I removed the xml/HTML and tested the button click ... it worked as expected.