What do you do with the processed data? If you are simply writing it back out as a new file (or replacing the original file), then you should read it with your Perl script a line at a time, process the line, then write it out. There are a couple of advantages in doing that. First you don't have to read and write the data multiple times. Second, you only read a (presumably) small amount of data at a time so the total memory used by your script remains small and doesn't start beating on the virtual memory system.

It may help if you show us the code that you are using.