Maternal cocaine injection causes fetal hypoxemia, hypertension, and increased cerebral blood flow (CBF) in sheep. To test the hypothesis that increased fetal CBF is not due solely to fetal hypoxemia, we injected cocaine directly into a fetal vein. A single dose of cocaine [1 (group 1; n = 7) or 2 (group 2; n = 8) mg/kg i.v.] was administered to chronically catheterized, unanesthetized, near-term fetal sheep. Fetal CBF (microspheres), arterial blood pressure (BP), O2 content, and cerebral O2 consumption (CMRo2) were measured at baseline, 30 s, and 2, 5, and 15 min after fetal cocaine injection. Fetal CBF increased 27 +/- 9% (SE) at 5 min in group 1 and returned to baseline by 15 min, whereas fetal CBF increased 57 +/- 8% at 5 min and remained elevated at 15 min in group 2. Fetal BP increased at 30 min in both groups and remained increased at 2 min in group 1 and at 5 min in group 2. Cerebrovascular resistance increased at 30 s in both groups and then decreased at 5 min only in group 2. Fetal hypoxemia was observed in group 2 5 min after cocaine injection (arterial PO2 decreased 24 +/- 5%), whereas no hypoxemia was noted in group 1. CMRO2 was unchanged in group 1 but increased in group 2 at 5 min (41 +/- 10%) and was associated with an increase in cerebral O2 extraction. Increases in myocardial and adrenal blood flows and reductions in both small and large intestinal blood flows were noted at 5 min in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)