The aim of this study was to examine the role of the central dopaminergic system in the mechanisms by which opioid peptides exert their influence on luteinizing hormone (LH) secretion in man. The effects of sulpiride and naloxone on the changes in LH secretion induced by a metenkephalin analog (D-Ala2-MePhe4-Met-(o)-ol-Enkephalin, FK 33824, Sandoz, Basel, Switzerland) (DAMME) and dopamine infusion in four castrated men (21 to 25 years of age) were studied. In these patients, sulpiride pretreatment counteracted the inhibitory effect of dopamine but did not alter the fall of LH plasma levels that DAMME induced. Moreover, in these subjects naloxone reduced the inhibitory effects induced by DAMME but did not change the inhibitory effect of dopamine on LH secretion. These findings confirm that central dopaminergic and opiatergic systems play a role in the control of LH secretion; the data also exclude any interaction between these systems in regulating LH secretion.