The endogenous opioid beta-endorphin (beta E) enhances, decreases or has negligible effects on cytotoxic and proliferative responses of lymphocytes. In order to characterize the mechanisms by which beta E modulates lymphocyte functions, we have examined the effects of beta E on certain membrane transduction events. We have shown that beta E inhibits phosphoinositol phosphate metabolism, and that it can enhance or inhibit the phosphorylation of the gamma chain of CD3 in a dose-dependent manner. We present the hypothesis that beta E contemporaneously modulates several membrane transduction processes, some of which may be counteracting and thereby producing the observed mixed effects on many lymphocyte functional responses. The biochemical status of the donor's lymphocytes also contributes to the variability in beta E-mediated effects on CMI outcomes.