To test the postulate that endogenous opioid peptides may be involved in the neuroendocrine mechanisms controlling the frequency and amplitude of LH pulses, saline and an opioid receptor antagonist, naloxone, were infused sequentially, each for 6-h intervals, in six normal cycling women during the luteal phase of the menstrual cycle. During naloxone infusion (1.6 mg/h), there was a significant (P less than 0.01) increase in both the frequency and amplitude of LH pulses compared to those in saline controls. FSH pulses were not discernible in individual subjects; however, a significant increment in FSH levels occurred concomitantly with the increase in LH. These data strongly suggest that endogenous opiates, through an inhibition of hypothalamic LRF, participate in the endocrine events leading to the low frequency of episodic LH secretion characteristic of the luteal phase of the human menstrual cycle.