Slow File System performance

We have a Windows 2000 Server on an IBM X346 attached to a 4TB DS400
Storage. This server acts as a Databse Server for an Animation application.

Problem is that users sufferer intermittent disconection from the server and
even file acccess from the server gives "not responding" errors. This Server
is connected to a gigabit L3 Switch and all the clients are connected to 3
24 port gigabit switches. Network seems to be fine, we suspect some OS
configuration or file system problems. All client access just stops and then
after some minutes everything is back to normal!

Last week we disabled "opportunistic locking" by editing the registry in the
Server and all clients, performance was good and now it is back to how it
was.

How do I find out exactly what is causing this problem? Any one has
experiences similar issues?

thanks
anth.