Estrogens exert both inhibitory and stimulatory effects on the secretion of GnRH and gonadotropins in women. The endogenous opioid peptides seem to mediate, at least in part, the inhibitory action exerted by estrogens on LH secretion. However, the mechanisms that mediate the stimulatory effect of estrogens on LH secretion are still unclear. The present study was performed to evaluate whether the endogenous opioid peptides could also participate in the stimulatory effect that estrogens exert on the gonadotropin response to GnRH. In postmenopausal women, a GnRH test was performed both under basal conditions and during the second month of treatment with transdermal 17 beta-estradiol (E2). In untreated postmenopausal women, two different doses of naloxone infusion failed to modify the LH and FSH responses to GnRH stimulation. During treatment with transdermal E2, the LH response to GnRH was significantly increased, while the FSH response was similar to that before treatment. Naloxone completely counteracted the enhanced LH response to GnRH observed during E2 treatment. On the other hand, naloxone did not significantly modify the FSH response to GnRH. The present results confirm that E2 exerts a sensitizing effect on the pituitary LH response to GnRH and suggest that the endogenous opioid system could be involved in this effect.