I cannot find correct repro steps for this, but:

/Library/Frameworks/Python.framework/Versions/2.7/bin/python" -B -s -c "import sys;print('%d.%d' % tuple(sys.version_info)[:2])
Traceback (most recent call last):
  File "/Library/Frameworks/Python.framework/Versions/2.7/lib/python2.7/site.py", line 558, in <module>
    main()
  File "/Library/Frameworks/Python.framework/Versions/2.7/lib/python2.7/site.py", line 540, in main
    known_paths = addusersitepackages(known_paths)
  File "/Library/Frameworks/Python.framework/Versions/2.7/lib/python2.7/site.py", line 264, in addusersitepackages
    user_site = getusersitepackages()
  File "/Library/Frameworks/Python.framework/Versions/2.7/lib/python2.7/site.py", line 239, in getusersitepackages
    user_base = getuserbase() # this will also set USER_BASE
  File "/Library/Frameworks/Python.framework/Versions/2.7/lib/python2.7/site.py", line 229, in getuserbase
    USER_BASE = get_config_var('userbase')
  File "/Library/Frameworks/Python.framework/Versions/2.7/lib/python2.7/sysconfig.py", line 518, in get_config_var
    return get_config_vars().get(name)
  File "/Library/Frameworks/Python.framework/Versions/2.7/lib/python2.7/sysconfig.py", line 421, in get_config_vars
    _init_posix(_CONFIG_VARS)
  File "/Library/Frameworks/Python.framework/Versions/2.7/lib/python2.7/sysconfig.py", line 300, in _init_posix
    raise IOError(msg)
IOError: $MACOSX_DEPLOYMENT_TARGET mismatch: now "10.3" but "10.5" during configure

Python was built on a Snow Leopard machine with MACOSX_DEPLOYMENT_TARGET=10.5 environment variable. But on the user's 10.6 machine, no such environment variable is necessarily set.

Why is this check required? Shouldn't it be restricted to building modules using distutils, and not happen during an innocuous "import site" that happens in interpreter startup?