To determine whether a gonadotropin-releasing hormone agonist could cross the placenta to the fetus, each pregnant rhesus monkey (110 to 155 days' gestation, n = 10) and her in utero fetus had indwelling cannulas placed in the femoral veins. Gonadotropin-releasing hormone agonist (1000 micrograms intravenously) was injected into the mother (n = 8) or fetus (n = 2); serial blood samples were collected from mother and fetus for luteinizing hormone and follicle-stimulating hormone determination. None of the mothers responded to the gonadotropin-releasing hormone agonist bolus. In contrast, some of the fetal monkeys receiving gonadotropin-releasing hormone agonist via placental transfer and all fetal monkeys injected directly with the agonist responded as indicated by increased luteinizing hormone (2.8- to 12.3-fold) and follicle-stimulating hormone (1.5- to 8.9-fold) concentrations. In evaluating maternal and fetal effects, we found that continuous maternal infusion with either gonadotropin-releasing hormone agonist (n = 14) or saline solution (n = 11) throughout pregnancy did not alter maternal hormonal profiles. Histologically, gonads from their infants, removed within 3 days post partum, were normal. Although neonatal ovarian weights were unaffected by the in utero treatment, the testes weighed less (p less than 0.05) in male infants born of mothers treated with gonadotropin-releasing hormone agonist compared to controls. Thus gonadotropin-releasing hormone agonist can cross from maternal to fetal circulation, and the fetus can respond (at least during the third trimester).