Sorry, I forgot to include a snippet because my wife was rushing me out the door. ;-) No, I'm not reading the whole file into an array; I'm using scalar context to read in one line at a time:

...
   open (INPUTFILE, $inputfile) or die ("\nERROR: Unable to open file 
+\"$inputfile\".\n");
   while (!eof(INPUTFILE))
      {
      $line = readline(INPUTFILE);
...
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And that's where it chokes. If I insert a print statement before and after the readline (as checkpoints), the first one will work, and the second one will not. I don't have experience using read, and when I tried replacing the readline with a simple read earlier, It looked like the same hang was happening. However, when I tried it again just now, it worked fine:

   read(INPUTFILE, $x, 1);
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Since I knew (from MUCH smaller files) that the input files would have chunks of chr(0) at the front, I wrote a bit of code around the read statement above to see just how bad the situation is for this particularly large file. As I write this message, we're at 120MB worth of continuous chr(0) and counting...