Experiments were undertaken in rats to investigate the effects of in vivo infusion of beta-endorphin (BEP) on subsequent Con A-induced proliferation and interleukin 2 (IL-2) production by spleen cells in vitro. BEP administration induced a dose-dependent enhancement of the proliferative response to Con A. Infusion of the opiate antagonist naloxone (NAL) inhibited the Con A response and infusion of NAL prior to BEP resulted in even further inhibition. None of these treatments resulted in detectable alterations in IL-2 production after 48 h in culture. To demonstrate a direct interaction between BEP and lymphocytes, spleen cells were incubated in vitro with varying concentrations of BEP and/or NAL. Enhanced Con A-induced proliferation was observed following incubation with BEP in the range 10(-12) to 10(-9) M (levels comparable to the effective in vivo doses) and this effect was abrogated by NAL pretreatment (10(-6) M). These data indicate a role for BEP in enhancing lymphocyte reactivity which is to some extent dependent on opiate receptors on the cell surface. This report extends the evidence obtained from in vitro experiments implicating endogenous opioids in modulation of host immunity by demonstrating that these effects can be obtained in vivo.