My mail box is currently 700 MB on disk and Thunderbird uses less than 100 MB of memory.
Thunderbird with a huge mail archive open: 1.5 G total, 500 M resident.
Does Thunderbird mmap it's mail archive or something? Because 1.5 GB sounds insane. Apple's Mail.app is only using 130 MB for a 1.8 GB mailbox. Might be an unfair comparison if Mail.app is leaning on the system for indexing/search (then again mds+mds_stores is using around 200 MB)
The metadata database for open folders is entirely resident in memory.