File size limitations are almost always an operating system limit, or at least a filesystem limit, and not a limit of "application" level systems like Perl.

On top of that, filesystems often allow files larger than what can be seeked (with standard runtime library calls), so it depends on how you're using it. A trivial program may only be able to randomly access the first 2GB of a file, while a streaming application (such as tar, gpg or a video player) can build and read many gigabytes sequentially.

What operating system, what filesystem, and how are you dealing with the file?

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