This is perhaps related to this question, but I have slightly more information.
I recently updated an ASP.Net application to .NET 3.5 after coding a few new pieces with Linq. Now my pages intermittently stop firing event handlers. I have it narrowed down to pages with Ajax on them, and I assume it's either the ScriptManager or the AjaxControlToolkit registration that is precipitating the problem.
The really screwy part is that pages seem to work fine about 2/3s of the time, and the controls lose their event handlers only 1/3 of the time. I wondered about some type of error occurring and the page not rendering correctly, but I cannot find evidence of this.