Thanks for the pointer, jasonk++.
I guess I'd eventually stumble upon this but you saved me a lot of time. :)

In case someone needs this in the future, the following works for <2GB files on HPUX 11

use Fcntl;
use POSIX qw(:unistd_h);
...

# $fh -- open file handle
# $lock is the structure that will be passed to fcntl().
# Note that values in the structure must be valid even 
# though they are not required for F_GETLK. If you just
# zero-out everything fcntl() will return "Invalid argument"
my $lock = pack 'sslli', F_UNLCK, SEEK_SET, 0, 0, 0;

# Second parameter - 5, represents F_GETLK. I couldn't use
# F_GETLK directly because it is mapped to 8 (F_GETLK64) and
# I couldn't get the definition for flock64 (the equivalent
# of "flock" for large files). The reason F_GETLK64 is 
# mapped to F_GETLK is because perl was compiled with
# USE_LARGE_FILES.
if (fcntl($fh, 5, $lock)){
   my $lpid = (unpack 'sslli', $lock)[-1];
   if ($lpid){
      print "File is locked by PID: $lpid\n";
   }else{
      print "File is not locked\n";
   }
}else{
   print STDERR "fcntl() failed: $!\n";
}

...
[download]

What I still don't know, and would be grateful if someone could point me in the right direction, is where flock64 is defined and what it looks like.
"/usr/include/sys/fcntl.h" includes "/usr/include/sys/_flock_body.h", which defines flock64 as:

  short l_type;
  short l_whence;
  long long l_start;
  long long l_len;
  unsigned int l_pid;
[download]

which should make the structure be 24 bytes long.
So, I packed it as 'sslllli' and got a nice "possible memory overflow" message after calling fcntl()... :/
To figure out what was going wrong I wrote a small C program, defined "_APP32_64BIT_OFF_T" to enable large file support, and did a sizeof() on the structure. Turns out it's 32 bytes long. Memory dumps showed that the structure looks something like this:

  short l_type;       /* 2 bytes */
  short l_whence;     /* 2 bytes*/
  long four_byte_foo; /* what's this? */
  long long l_start;  /* 8 bytes */
  long long l_len;    /* 8 bytes */
  unsigned int l_pid; /* 4 bytes */
  long four_byte_bar; /* what is this? */
[download]

So, I'm not sure where those extra 8 bytes come from. They look suspiciously like padding, to make sure everything's on a 64-bit boundary, but I'm not entirely sure...

As a side note, direct usage of fcntl() makes your program unportable even among UNIX systems. Linux, SunOS, BSD -- they all have different flock structures and Windows doesn't even support fcntl().

--perlplexer