Cocaine is a potent vasoconstrictive agent that is currently the subject of widespread drug abuse. Because little is known of the physiologic responses to cocaine in pregnancy, the effects of intravenous cocaine on uterine blood flow and other maternal and fetal cardiovascular parameters were studied. Eight ewes in late pregnancy were equipped with electromagnetic flow probes around both uterine arteries and catheters were placed in the maternal and fetal inferior vena cavae and aortas. Bolus intravenous infusion of 0.5 and 1.0 mg/kg of maternal body weight achieved peak plasma cocaine levels similar to those observed in human subjects after abuse of the drug (mean level = 229 to 400 ng/ml, n = 8). After bolus infusion of 0.5 or 1.0 mg/kg of cocaine, mean maternal arterial pressure increased 32% and 37%, respectively (p less than 0.005). Fetal blood pressure rose 12.6% after a dosage of 0.5 mg/kg of cocaine. These cocaine infusions significantly decreased uterine blood flow by 36% and 42% for a duration of 15 minutes (p less than 0.005). Analysis of maternal catecholamine responses demonstrated a significant (210%) rise in plasma norepinephrine levels after cocaine infusion. These studies demonstrate that cocaine, when administered in doses that produce plasma levels observed in humans, significantly decreases uterine blood flow for a duration of greater than or equal to 15 minutes while inducing a hypertensive response in the pregnant ewe and fetus.