The best by far is to use one main mapfile and with the INCLUDE directive call other mapfiles. This will speed things up definitely, I tested that and the result is quite impressive. This idea comes from here: http://mapserver.org/es/optimization/mapfile.html

"If you have a complex application, consider using multiple simple and specific Map Files in place of one large ‘do everything’ Map File."

Check this very nice post and blog from Simon, he's a very nice guy working with mapserver and related things: http://smercier1.mapgears.com/blog/?p=37. I used these performance tips and they do work. Here you have another [link][1], but Simon basically explained that already in his blog.

Hope this helps,


  [1]: http://blog.cleverelephant.ca/2008/10/mapserverpostgis-performance-tips.html