Cocaine abuse during pregnancy is associated with adverse perinatal outcome, believed to be a result of potent vasoconstrictive effects that cocaine has on the maternal cardiovascular system. The direct effect of cocaine on the pregnant, nonhuman primates' uterine vasculature in vivo has not been examined. We investigated the effects of intravenous cocaine on maternal arterial blood pressure, uterine blood flow, and uterine vascular resistance in four unanesthetized, chronically instrumented pregnant baboons. Baboons were instrumented during the latter half of pregnancy, placing an ultrasonic flow probe around one uterine artery and catheters in the maternal inferior vena cava and aorta. Bolus intravenous cocaine hydrochloride doses of 0.05 mg/kg, 0.1 mg/kg, and 0.3 mg/kg by maternal weight were infused 30 minutes apart at least 5 days after surgical instrumentation. The maternal blood pressure rose 7.3% and 12.0% after the 0.1 mg/kg and 0.3 mg/kg cocaine infusions, respectively, and the uterine blood flow fell in a dose-dependent fashion 13.1% and 22.7%. Plasma norepinephrine levels rose in response to the 0.3 mg/kg cocaine infusion. These studies show that low doses of cocaine significantly reduce uterine blood flow in the pregnant baboon in a dose-dependent manner by increasing uterine vascular resistance.