Both drives are internal.
I'm running a 1.5TB Seagate Barracuda with music etc on, a 750GB Samsung SpinPoint with programs on and then 1 120GB OCZ Vertex 3 with OS and PS on.
The only drive that seems to be having this problem is the Seagate one. Just to reiterate what is happening:
When the drive is accessed after a while (this can be opening a folder or using iTunes), it has a period of lag where nothing can be clicked (the computer does not freeze, just explorer). After a few seconds, and with a "reassuring" click-type sound, the drive starts to work and continues as normal.