The effects of melatonin on LH and PRL releases induced by treatment with naloxone, naloxone methyliodide and nalmefene were studied in adult male rats. Subcutaneous melatonin injection (1.4 mg/Kg) had no effect on LH secretion, but caused an inhibition effect (84%) on LH release induced by naloxone (2.4 mg/Kg). Melatonin too totally inhibited LH secretion induced by naloxone methyliodide (2.8 mg/Kg) and nalmefene (2 mg/Kg) when it was simultaneously administered with each opioid receptor antagonist. Melatonin alone had no significant effect on serum PRL levels, but decreased by 25.5% the inhibitory effect potency of nalmefene on PRL secretion after simultaneous injections. The inhibitory effect potency of naloxone on PRL release increased (16%) when it was administered with melatonin. Simultaneous injection of melatonin with naloxone methyliodide inhibited PRL release (78%) while naloxone methyliodide alone did not modify this secretion. The results obtained with a quaternary opioid antagonist indicate that the opioid receptor type which mediates LH and PRL responses is located respectively outside and inside the blood-brain barrier. Our findings show that opiate antagonists and their quaternary ammonium salts affect secretion of LH and PRL through different mechanisms susceptible to the influence of melatonin.