The POMC-derived peptides beta-endorphin and ACTH are capable of modulating an immune response in physiological concentrations. These neuropeptides can either enhance or inhibit the proliferative response of human peripheral blood lymphocytes after stimulation with the mitogen concanavalin A. The modulatory action of the peptides is not only dependent on the concentration but appears to be donor dependent. The response pattern observed is not determined by a selective affinity for certain amino acid sites on the molecules with "enhancing" or "inhibiting" activities, since fragments of beta-endorphin and ACTH also produce a differential donor-dependent response pattern.