It has been found that beta-endorphin (beta-END) and a synthetic beta-END-like decapeptide Ser-Leu-Thr-Cys-Leu-Val-Lys-Gly-Phe-Tyr (termed immunorphin, IMN) corresponding to the sequence 364-373 of human IgG heavy chain stimulate Con A-induced proliferation of T lymphocytes from the blood of healthy donors. [Met(5)]enkephalin ([Met(5)]ENK) and an antagonist of opioid receptors naloxone (NAL) tested in parallel were not active. The stimulating effect of P-END and IMN on T lymphocyte proliferation was not inhibited by NAL. Studies on receptor binding of 125 I-labeled IMN to T lymphocytes revealed that it binds with high affinity to NAL-insensitive binding sites (K-d = 7.0 +/- 0.3 nM). Unlabeled beta-END completely inhibited the specific binding of 121 I-labeled IMN to NAL-insensitive binding sites on T lymphocytes (K-i = 1.1 +/- 0.2 nM). Thus, beta-END and IMN bind to common NAL-insensitive binding sites on T lymphocytes and enhance Con A-induced proliferation of these cells. (C) 2002 Elsevier Science (USA).