I'm running SpamAssassin 3.0.1 on a Compaq Alpha running Tru64-Unix, sendmail 8.12.10. I have been running SA for about 6 - 8 months on a few test accounts with great success. I tried to set it up so it would filter all of my system email for about 2500 accounts. When I set it up email in the queue start to back up. For instance when I started it I had 20 items in the queue and after I started SA the number went to 130 in about 30 minutes. Anything I sent then appeared to be being worked on but they couldn't be sent.
After I stopped SA then everything cleared out of the queue in about 10 minutes.
How are you calling SA? just as spamassassin in procmail, or are you using spamd, or an integration tool like mimedefang?
How you call SA is a VERY critical detail to performance. It's hard to make suggestions other than broad generic suggestions:
if you're using any add-on rulesets, consider deleting all the large ones (any .cf file over 256k can be a problem and should be carefully tested for load impact on your system prior to deployment)
if you have limited CPU power and ram, consider disabling the AWL and/or bayes.
if you have slow network access consider disabling RBLs.
There's lots of specific suggestions however:
if you're calling spamassassin via procmail, switch to using spamc in procmail and start spamd. spamc/spamd is MUCH faster than plain spamassassin.
if you're using spamd, tune the -m parameter to suit the amount of memory you have. Too many children and you exhaust memory and swap. Too few and you're not going as fast as you could.