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 < 0.05) following cocaine injection. No changes were seen in maternal pCO₂ 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.