Generally, such a problem may occur if the number of CSS files registered on the page increases beyond 31 - this is an Internet Explorer limitation. If the issue occurs in all browsers, then it has something to do with AJAX functionality - for example regular asp:UpdatePanels are unable to update the <head> of the web page, where CSS files are registered.
If the problem occurs with RadAjaxPanel or RadAjaxManager, please send a simple runnable demo and we will inspect it.
All the best,
the Telerik team