Naloxone (10 mg) was given intravenously to seven postmenopausal women not receiving hormone treatment and to six postmenopausal women receiving Premarin-Provera treatment during the Premarin phase and also during the Premarin-Provera phase of therapy. Baseline estrone and estradiol levels (mean +/- SEM) were significantly lower in the group not receiving hormones (46.0 +/- 5.2 pg/ml and 28.4 +/- 3.1 pg/ml, respectively) than in the group in the Premarin phase of therapy (154 +/- 14 pg/ml and 79 +/- 13 pg/ml) and the group in the Premarin-Provera phase (135.1 +/- 8.3 pg/ml and 57.5 +/- 3.0 pg/ml) (p less than 0.005). Follicle-stimulating hormone, luteinizing hormone, and prolactin levels were 118.7 +/- 5.3 mIU/ml, 118.7 +/- 9.5 mIU/ml, and 9.2 +/- 0.7 ng/ml, respectively, with no significant change after naloxone administration in untreated women. With hormone therapy the basal follicle-stimulating hormone and luteinizing hormone levels decreased significantly while basal plasma estrone and estradiol increased significantly. In both the group in the Premarin phase of therapy and the group in the Premarin-Provera phase, luteinizing hormone levels increased significantly at 30 (135% +/- 10%, 144% +/- 8%), 45 (150% +/- 12%, 133% +/- 11%), 60 (149% +/- 15%, 128% +/- 11%), and 90 (139% +/- 15%, 132% +/- 13%) minutes after naloxone administration (p less than 0.01 to p less than 0.001). Follicle-stimulating hormone levels did not change significantly whereas prolactin levels showed a trend toward a decrease. These findings indicate that opioid inhibition of gonadotropins is reduced in postmenopausal women but increased with Premarin-Provera treatment. The effect of sex steroid on the opioid system in the postmenopausal women differs from that in the premenopausal women.