The problem, I think, is in this statement:
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The xbox w/ 2.2.1 and the 300 gb does not work w/ the big hard drive in. The OS will boot, but none of the drive features work. I can not unlock the drive, or format any of the partitions. The drive upgrade wizard fails.
How did this drive get locked? You will not be able to format it, or do anything with it for that matter, until it is unlocked.
Ahh...
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PS. I put some BIOS files on the 300 gb drive when it was attached to the working xbox. When I tried to add a launch item on the non-working xbox the screen where you select the files was completely blank - it could not read the hard drive...
You must have locked the drive on the 1st box ... put it back in there, unlock it, then move it to the 2nd box. Problem solved.