I have 192 299 messages currently in my PowerMail DB and I experience no slowdown in 3-pane view, though mostly I read from an opened message of the recent messages window. Saving a message sometimes take far too long, like 10 seconds or so.
I compact my DB like once a month, going from 1.8GB to about 800MB. As for your problem, Jim, I wonder if much of yor email is HTML-based? Perhaps that affects speed negatively. PM 5.2.1 | OS X 10.3.9 | Powerbook G4/400 | 768 MB RAM | 30 GB HD