This may be the wrong forum to look for an answer, but I thought I would start here. We have been using BLAT on G4 Xserves (2GB RAM) for some time now. Given the memory limitations, we carve up the database into chunks so that we don't get a malloc error message telling us we have run out of huge memory. We then parallelize the job and run the chunks in parallel on our cluster. This works for modest query sizes (15,000 ESTs vs 1.2GB database-hs_chroms1-6). However, when we scaled up to larger queries (493365 ESTs vs 1.3GB database-bovine genome 200,000scaffolds) we see blat just sort of stop working after a while. I ran the leaks program and found 91832 memory leaks, so the problem seems to be memory related. I would be curious to know if anyone else has seen this type of behavior with BLAT. I am in the process of contacting Jim Kent about this, but thought it would not hurt to ask some other knowledgeable computational biologists about this. thanks in advance, Dave Adelson Texas A&M University