It has been found that β-endorphin (β-END) and a synthetic β-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. [Met5]enkephalin ([Met5]ENK) and an antagonist of opioid receptors naloxone (NAL) tested in parallel were not active. The stimulating effect of β-END and IMN on T lymphocyte proliferation was not inhibited by NAL. Studies on receptor binding of 125I-labeled IMN to T lymphocytes revealed that it binds with high affinity to NAL-insensitive binding sites (Kd = 7.0 ± 0.3 nM). Unlabeled β-END completely inhibited the specific binding of 125I-labeled IMN to NAL-insensitive binding sites on T lymphocytes (Ki = 1.1 ± 0.2 nM). Thus, β-END and IMN bind to common NAL-insensitive binding sites on T lymphocytes and enhance Con A-induced proliferation of these cells. © 2002 Elsevier Science (USA).