To assess the effects of cocaine, administered to the ewe, on the secretion of atrial natriuretic peptide (ANP), Plasma Renin Activity (PRA) and hypoxanthine in the fetus we studied 6 chronically cannulated sheep fetuses late in gestation. The ewe was given an intravenous injection of cocaine (2 mg/kg). Maternal and fetal arterial blood samples were withdrawn prior to the injection and at 2, 5, 10, 15, 45 and 60 min after the injection for the measurement of ANP, PRA and hypoxanthine. Fetal arterial blood pressure (MAP), plasma ANP and protein levels increased and pH and pO2 decreased after cocaine was administered to the ewe. Fetal plasma hypoxanthine and PRA did not change. These results suggest that cocaine administration to the ewe is associated with fetal hypertension, hypoxemia and acidemia all of which may serve as stimuli for the secretion of ANP.