In the present paper we demonstrate that one of the early effects of the opioid peptide beta-endorphin on human peripheral blood mononuclear cells is the induction of a change in the intracellular cAMP level. However, the effect of beta-endorphin on cAMP levels is not uniform; increases as well as decreases in cAMP level are observed. It appears that beta-endorphin is a true modulator of intracellular cAMP level: the peptide will increase cAMP levels in cells with a low baseline level. In contrast, beta-endorphin tends to decrease cAMP levels is cells with a high cAMP concentration. Moreover, beta-endorphin modulates the rise in cAMP induced by beta-adrenergic activation. The effect of beta-endorphin on cAMP level correlates negatively with the magnitude of the change in cAMP level induced by beta-adrenergic activation.