Thanks Shane. Is all of your suggestions along with the setup I was considering? I have to research ZEO, cause I know nothing about it. Do you mind explaining the last two things just a slight more as I am unfamiliar. Such as how you figure out cache and what is packing?
FileStorages only append until you pack. Visit the database control panel to remove old versions of objects. No wonder your database is big--since you've never packed, your database contains all revisions ever committed. Packing will help a lot.
To figure out the right cache size, start with 4000 (as you have done.) Let your site run and look at the activity graph for each database after an hour of peak usage. If it's loading a lot of objects on every request, increase the cache size to use more RAM (but don't make Zope swap!) If it's hardly loading anything, decrease the cache size to give RAM back to the system.
Mounting portal_catalog is a new trick I've been asking people to try. Just put it in a mounted database. Once you've done that, your main database will probably grow much more slowly than before.
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