AbstractMet-enkephalin (ME) in the range of concentrations 10−15M to 10−9M has exhibited an immunomodulating effect on concanavalin A (Con A) induced proliferation of mice lymphocytes from lymph nodes in vitro. The effect of ME was shown to vary with the stage of lymphocyte activation and to depend on the mitogen dose. In the case that ME and Con A were injected simultaneously, at the zero time of proliferation, maximum inhibition was observed on the first and fourth days. In an other set of experiments when ME was added at intervals of 4 hours before measuring the proliferation response value, both inhibition (after 24 hours of proliferation) and stimulation (after 28 and 96 hours) were observed. Opioid ligands of various classes were found to act in the same manner as ME. Naloxone was shown to block the immunomodulating effect of opioids.