My solution to stop wordpress comment spam is a combination of three Wordpress plugins:
Akismet has protected your site from 11,247 spam comments already, but there's nothing in your spam queue at the moment. Since its last activation on May 25, 2010
NoSpamNX has stopped 385 birdbrained Spambots (17 per Day).
2,391 spam comments have been automatically discarded by the Conditional CAPTCHA plugin.
Since the time I started using this combination a few months ago, I have only had about 3 spam comments in my comment queue.