I was initially running 2 graphics cards before I began 5 boxing, I ended up having to go down to 1 because of the Windows XP Horizontal Span issue. The option apparently (at least for me) isn't available unless you are only using one card.
After I upgraded to Vista (because I HATE horizontal span) I assumed I could put my other card back in. After doing so, I noticed a dramatic drop in my FPS. I'm not sure what caused this, I checked my drivers and setup and everything was the same, but my FPS was just down the toilet. I ended up taking out my second card altogether and currently run off just a single card and am doing quite well though. I average 40-50 fps on my primary with maxed settings, and cap my clones to 15 while in the background. This is all on a 7600 GT card.
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