Chronic alcohol abuse in women is associated with severe derangements of menstrual cycle regularity. However, acute alcohol ingestion has no effect on pituitary-gonadal secretory function. The purpose of this study was to determine whether acute alcohol ingestion altered the effects of naltrexone, a long-acting opioid antagonist, on pituitary, adrenal, and gonadal hormones in normal women. Fourteen women were studied during the early follicular phase (between days 2 and 4) of their menstrual cycle. Plasma LH, PRL, estradiol, progesterone, and cortisol concentrations were measured before and after administration of 50 mg naltrexone, orally, and alcohol or placebo solution given 1 h after naltrexone, under double blind conditions. Naltrexone significantly increased mean plasma LH (P = 0.02), PRL (P = 0.003), E2 (P less than 0.03), and cortisol (P less than 0.001) levels. Alcohol significantly augmented the naltrexone-stimulated increases in plasma LH (P = 0.006), estradiol (P less than 0.004), and cortisol (P less than 0.001) levels and significantly decreased plasma progesterone levels (P = 0.001). Plasma PRL increased (P = 0.001) to the same extent after naltrexone and alcohol ingestion or naltrexone and placebo. We conclude that alcohol enhances naltrexone-induced increases in plasma gonadotropins and adrenal and gonadal steroid hormones in women during the early follicular phase of the menstrual cycle.