Dopaminergic activation has been reported to either stimulate, inhibit, or have no effect on hypothalamic GnRH secretion. We used in vitro incubation of male rat arcuate nucleus-median eminence (ARC-ME) tissue to demonstrate that 1-mu-M dopamine (DA) inhibited GnRH release, 0.4 mg/ml of the opiate receptor antagonist naloxone (NAL) was without significant effect, but DA + NAL stimulated GnRH release. The DA receptor antagonist haloperidol but not the alpha-adrenergic receptor antagonist phentolamine blocked inhibition of GnRH release by DA as well as stimulation of GnRH release by DA + NAL. These results suggest that dopaminergic inhibition of ARC-ME GnRH release may be mediated by increased endogenous opioid activity and that blocking this increased opioid activity allows a stimulatory dopaminergic effect on GnRH release to be expressed.