Are you getting a "Not enough memory to load this image." error? Is the program refusing to create a new layer, or resize the image?
If you're getting a "file too large" error, your problem might not be what you think it is. Here's Rick's explanation, from another thread:
In addition,
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Please be aware that all of this was written prior to the release of PdN 4.0, and some things may have changed.