It is known that opiate administration results in the inhibition of LH release. In this paper, we examine the role of endogenous opiates in the regulation of gonadotropin secretion during the menstrual cycle of the monkey. The objectives of these experiments were to determine the experimental and endocrine conditions that are conducive to increased gonadotropin secretion in response to endogenous opiate antagonism. In Exp 1, naloxone was administered during the luteal phase to three groups of monkeys under three different experimental conditions. When naloxone (2 mg, iv) was injected into conscious unrestrained or sedated animals, LH secretion increased 2- to 3-fold. In contrast, the same dose of naloxone failed to stimulate LH secretion in monkeys restrained in primate chairs. In Exp 2, the gonadotropin response to acute naloxone administration on each day of the menstrual cycle was determined. A significant increase in the serum LH concentration (greater than or equal to 20% within 40 min of injection) was observed after naloxone administration in 60% of the trials conducted during the luteal phase. Significant increases occurred in only 13% of the saline-treated control trials during this stage of the menstrual cycle. Mean LH levels increased from 14.4 +/- 1.3 to 31.2 +/- 4.3 ng/ml after naloxone injection. In contrast, naloxone had no effect on LH secretion during the follicular phase. Although small LH increments were noted after naloxone injection in 40 +/- 8% of the trials, neither the frequency nor the amplitude of these increases was different from that in follicular phase controls. We conclude from these results that the ability of naloxone to stimulate LH secretion is limited to the luteal phase. Previous findings from our laboratory indicate that hypothalamic beta-endorphin activity, as reflected by its concentration in hypophyseal portal blood, is increased by ovarian steroids and that its greatest activity occurs during the luteal phase. Since the response of LH to naloxone administration was limited to the luteal phase, we believe that these results support the conclusion that hypothalamic beta-endorphin is a physiological modulator of LH secretion in the monkey.