OBJECTIVE Although maternal cocaine administration results in fetal cardiovascular and behavioral alterations, these responses have been attributed to hypoxia resulting from reduced uteroplacental blood flow. We studied the fetal catecholamine, cardiovascular, and neurobehavioral responses to direct fetal cocaine administration. METHODS Cardiovascular, electrocortical, and electroocular responses and plasma catecholamines were monitored in chronically catheterized fetal sheep (n = 7), 127 +/- 2 days' gestation, during a control period and after intravenous fetal injections of cocaine 0.5 and 1.0 mg/kg. RESULTS Intravenous cocaine caused prompt increases in fetal plasma norepinephrine (372 +/- 73 to 531 +/- 112 and 842 +/- 233 pg/ml), epinephrine (27 +/- 7 to 46 +/- 13 and 49 +/- 11 pg/ml), and systolic blood pressure (46 +/- 2 to 53 +/- 2 and 55 +/- 2 mm Hg). Low-voltage electrocortical activity decreased from 61.7% +/- 3.0% to 38.4% +/- 3.9% in the first hour after the cocaine 0.5 mg/kg dose but recovered to baseline values during the second hour. After the cocaine 1.0 mg/kg dose, low-voltage electrocortical activity decreased to 40.7% +/- 2.0% and did not recover thereafter. Fetal blood gas values did not change. CONCLUSIONS Direct fetal cocaine administration increases fetal plasma catecholamine levels and fetal blood pressure and suppresses low-voltage electrocortical activity. Chronic cocaine exposure may hamper central nervous system maturation and alter postnatal development.