Although cocaine administration reduces blood flow to the fetus in the pregnant ewe, the effects of cocaine on uterine and placental blood flow in the pregnant rat have not been adequately documented. The current study tested the hypothesis that cocaine decreased uterine and placental blood flow in awake and freely moving pregnant rats 17 min following gastric intubation. Blood flow was determined using [14C]iodoantipyrine in pregnant Sprague-Dawley rats 1 day prior to parturition. On the day of the experiment, rats were intubated with either 60 mg/kg cocaine or the vehicle and 17 min later infused i.v. with 75 microCi [14C]iodoantipyrine. Ten arterial blood samples were taken over 1 min through a femoral arterial catheter placed on the previous day. At 1 min the animal was decapitated and the entire uterus rapidly removed and frozen. After processing for autoradiography, the amounts of radioactivity in the tissues were determined by computerized image analysis. The results show that cocaine reduced blood flow in the uterus by 27% and decreased blood flow in the placenta by 30%. While cocaine reduced the total amount of iodoantipyrine reaching the fetus, the distribution of tracer within the fetus did not appear to be altered by cocaine. Maternal blood pressure and heart rate decreased by 5% and 13% respectively (paired t-test), while maternal and fetal blood gases were not altered. These data indicate that acute cocaine administration reduces uteroplacental blood flow in the rat. The duration of this effect and whether these decreases are sufficient to produce neurobehavioral changes in the offspring remain to be determined.