Few in vivo studies have been done to characterize the effects of cocaine on the maternal and fetal pituitary-adrenal axis during pregnancy. We, therefore, administered cocaine (2 mg.kg-1) intravenously to 6 fetal sheep at 127-138 days of gestation. There was a transient reduction in fetal arterial pO2 with a concomitant increase in pCO2 and a prolonged fall in pH (p less than 0.05) following cocaine injection. No changes were seen in maternal pO2, pCO2 or pH. Maternal adrenocorticotropin (ACTH), cortisol and lactate were not affected by fetal administration of cocaine. Although there was a tendency for fetal plasma ACTH, cortisol and lactate to rise after administering cocaine, the increases were not statistically significant. Previous studies have shown that cocaine administration to the ewe at a similar stage of pregnancy results in increased fetal plasma ACTH concentrations. The results of the present study indicate that cocaine administration to the fetus compromises fetal gas exchange and acid-base balance but the effects on the fetal pituitary-adrenal axis are less pronounced than after maternal administration of cocaine.