Beta-endorphin has been reported to enhance T lymphocyte proliferation and cytolytic activity. In this report, it is demonstrated that beta-endorphin enhances the production of the T cell lymphokine, interleukin-2, from mitogen-stimulated, unfractionated murine splenocytes, as well from a cloned T cell line. The enhancement is naloxone irreversible and dependent on the integrity of the C-terminal amino acids, though the N-terminal amino acids appear to contribute to the potency of the enhancement. The data suggest that beta-endorphin interacts with a nonopioid receptor that has specificity characteristics similar to a nonopioid beta-endorphin receptor described in the central nervous system.