Are you using Render Multiple Frames Simultaneously multiprocessing? If so, make sure that you've got enough RAM reserved for other applications, including the OS. Actually, I'd try just turning Render Multiple Frames Simultaneously multiprocessing off to see if that alone makes your problem go away.
A side note (perhaps not related to your issue): You didn't say whether you had installed the After Effects CS4 (9.0.2) update. That update fixed a lot of bugs.
No, I tried Render Multiple Frames Simultaneously, but it was very slow and erratic - much better leaving all that switched off, for me anyway.
In fact I experimented with alot of this when I upgraded to CS4 last year, but found by far the best performance was had by leaving it all off.
Compressed formats involved? If so, flushing the media cache might help.... I would also investigate graphics card settings. Could just as well be an issue with drawing priorities between programs that have somehow changed when flipping a switch.
Targas at the moment - mostly what I render from Lightwave.
Thanks - yes, I've been looking at the graphics card part of today. It definitely isn't the card itself, in terms of dodgy hardware as we tried an identical one from another machine, which performed the same.
It does have that look of a bottleneck after a more intensive operation, like a RAM preview.
Unfortunately, I am not very knowledgeable on what all those card settings are, but I guess one of them could be throwing things - updated the driver today as well, with still the same performance hit afterwards.