F5 LTM and Sharepoint

Brain storming here: Have you checked the IIS logs at the time and seen if requests is registered at all when the problems occur? Have you checked the event log? This one is a tough one but putting the site into maintenance and only allowing your IP while logging the traffic in Wireshark would also help. Then you could compare a working scenario with a non-working one. Test the server via curl like Kevin suggests, check the logs in IIS. Good luck! /Patrik