> We have about 2000 lists. A few have a lot of subscribers (over 10k),
> with a total of either 180k? 280k? registered names

This should take a second or two. I forgot:

4. You have an anti-virus program configured to scan *all file types* in
LISTSERV's directory tree ;-)

Ok, let's try this. Add the following to SITE.CFG:

DEBUG_FLAGS=1

Restart and do TIME QUERY * FOR <email address> and see what the log says.

My take is that LISTSERV opens a lot of .LIST files, which would not happen
to the same extent with HPO, and the AV takes its jolly good time applying
heuristics to the contents of these files, which it must think look like
Excel documents or whatever. Bonus points if you have one really large file
that allows the heuristics to explore hundreds of different paths before
finally giving up on a timeout with a nice error in the event log. Of
course, if these .LIST files *were* Excel documents, you probably wouldn't
mind (or notice) the scan when you opened them...

  Eric