OBJECTIVE Opioids generally suppress gonadotropin secretion. We investigated whether chronic opiate antagonism would affect the occurrence or timing of menstrual cycle events. METHODS Opiate blockade was maintained in nine normal volunteers from cycle days 1 through 13 with naltrexone. A double-blind, placebo-controlled crossover design was used. Serum estradiol and progesterone were measured daily. Vaginal ultrasonography was performed daily beginning cycle day 10. Endometrial biopsies were performed 10 to 12 days after ovulation. Nonparametric paired data analysis was used. RESULTS No significant differences in the following menstrual cycle parameters were detected between naltrexone and placebo cycles: cycle length (25.4 +/- 0.9 vs 25.7 +/- 0.5 days), maximum follicle size (21.5 +/- 1.0 vs 20.8 +/- 1.1 mm), peak serum progesterone (15.8 +/- 1.8 vs 15.2 +/- 2.2 ng/ml), or integrated serum progesterone (108.1 +/- 12.8 vs 101.2 +/- 14.6 ng/ml/day). Histologic endometrial development was normal in all subjects during naltrexone cycles. CONCLUSIONS These data suggest that naltrexone-suppressible opioid activity does not play a significant role in the regulation of follicular events in normal women.