Not knowing how you resolved your problem, I have to give two answers. If you are using files from the old Mapsend Topo USA, they were limited to four combined 16mb regions within a single file: 64mb total. Exceeding that by changing mapsend.ini parameters sometimes would work ok, but overly large files were prone to corruption (e.g., incorrect road names, or even outright failure to operate) and could create performance lags.
In MapSend Topo3D, these aspects were overcome fairly well. You create a single region for a single detailed map file, and it can be pretty freaking large...something like 229mb or something. There are no performance degradations I know of due to large files (although conducting address or POI searches on larger files are more cumbersome than in smaller files since there is more stuff to sift through). Make the file as large as you want; if MapSend says you are going too big, though, I would heed the warning.
Edit: I peeked in the Mapsend.ini file and saw the parameter "Conv_Memory_Size=246784," which I take to be the maximum region size in KB. I don't know of anyone editing that to allow larger files, but that's already huge. One other slight downside of larger files I didn't mention above is that they can take very long times to compile.
I resolved my first problem by exchanging V4.2 for 3D, now everyhing is working great. I created a few regions with the file size being around 30,000KB and I was just wondering if I should keep them smaller than that or if I could even go much bigger, because I couldn't really find any info on how big they should be.
Thanks for your help!