I don't know what's happening with your system but I spent a few minutes looking into this on a Win 7 64 bit system with 16GB RAM. I see that memory usage increases according to how big and how many layers the file has when I open a file. If I add layers, etc., the memory usage increases as you'd expect. When I close the file, but leave Photoshop CS5 open, the memory according to task manager stays allocated (shows no decrease in amount used). If I close Photoshop CS5 the memory usage decreases to what it was before I first opened Photoshop. If I understand your post correctly your system appears to not be releasing this memory even when you close Photoshop. I wonder if you try what I described here, without letting the system get to a point where it's slowing down, if it works similarly. It may be that there's a bunch of scratch disk being used and memory has gotten tight, and it's just taking a very long time to release memory and remove scratch files.