Endogenous opioid peptides tonically inhibit LH by acting on hypothalamic mechanisms which regulate LHRH secretion. Opiates increase hypothalamic serotonin turnover but the involvement of the serotoninergic system in the opioid mechanisms regulating LH secretion in man is not clear at present. This study was designed to evaluate whether the tonic inhibitory effect on LH secretion induced by opiates involves the serotoninergic system. We have studied 10 healthy young men (aged 20-28 years). Five subjects were infused with naloxone (10 mg/h for 3 h) before and 120 min after fenfluramine administration (60 mg orally) on two different occasions. In five other subjects naloxone was infused before and after metergoline pretreatment (8 mg on first and second day and 4 mg on the third day, orally, at 0 time of naloxone infusion). After fenfluramine, naloxone infusion failed to induce any increase in LH plasma levels; metergoline pretreatment significantly enhanced the naloxone-induced LH increase. These data suggest that in man a hypothalamic serotoninergic system may be involved in the opioid mechanisms regulating LH secretion.