If you haven't yet, I suggest you get into the habit of backing up your profile. You should also add Thunderbird's Profiles folder to your antivirus program's exclusions list. Are you sharing this profile with another installation of Thunderbird, say on a Linux system or some other computer?

I do back up my profile fairly regularly (both online and using MozBackup) and I'm not sharing the profile. I'll check and see about the antivirus, though. Thanks.

As an update: I added an exception on Avast and it didn't change anything. Then I uninstalled and reinstalled Thunderbird and restored my profile and that didn't fix anything, either.

I don't understand this. This might have to be the end of the road for me and Thunderbird. Sigh.

You could try a new Thunderbird profile, then migrate the individual data files (mbox, mab, msgfilters) from the old profile to the new one. This will hopefully fix the problem IF it is an issue with a corrupt profile. With the "hell" that the PC is giving you, it's not hard to imagine profile corruption as the cause.

I'll give that a shot--thanks. (The hell has been other stuff completely unrelated to Thunderbird--memory issues and a headphone jack I can't figure out how to get working again.)

Welp, about 24 hours later the msf files have disappeared again. Between this and address book issues and Signature Switch suddenly ceasing to work, I guess it's goodbye, Thunderbird. It's been a good 15 years.

I highly doubt this has anything to do with Thunderbird, but that's of no import now, so, fare thee well.

I just have no idea what to do. The only thing left to try is to see what happens if I transfer the data to a fresh install of Thunderbird on a different machine, which I can attempt later.

Coming back to say that removing my Gmail accounts from Thunderbird seems to have fixed the issue--for unknown reasons, the .msf files would disappear when Thunderbird tried to sync Gmail. I mainly use the web interface for that anyway, so it wasn't a loss.

GMail has a nasty habit of notifying Thunderbird that entire folders are "out of date" and needs to be brought up to date. So not just the MSF disappears, in my case with local copies it downloads the entire folder over again. Most helpful with things like "All mail"

All my Gmail IMAP accounts on Tbird are configured to download headers only, except for the account I use with this and other forums, which I've configured to synchronise only 7 days worth of emails in the inbox folder. This keeps the Inbox mbox file roughly about 2MB in size.