With large numbers of users and many channels, I might suggest checking your buffer size and make sure it's not too large. That's in mIRC's option at the bottom (Display, I believe). If the buffer is really large and you have many channels that are active, it can really slow things down. For most people, 1000 is plenty, but some like more and some like less than that. You might also check what your logging settings are. If you're logging a lot of lines at once, it's possible to get some lag.
Though, I think I read that it actually locks up permantly until you exit it? If that's the case, I'm not really sure. These would mainly be things that might potentially cause a temporary freeze (just like antivirus could).