The authors tested the hypothesis that in the high-altitude acclimatized fetus, hypercapnia has a significantly less effect on cerebral blood flow (CBF) and cerebral oxygenation than that in normoxic sea level controls. In the high-altitude acclimatized fetus (3801 in; maintained from day 30 of gestation to near term; n = 6), by use of a laser Doppler flowmeter with a fluorescent O-2 probe, the authors measured relative CBF (laser Doppler CBF [LD-CBF]), cortical tissue PO2 (tPO(2)), and sagittal sinus oxyhemoglobin saturation (HbO(2)) in response to 20-minute hypercapnia. They also calculated cerebral O-2 delivery and cerebral fractional O-2 extraction. The authors compared these results to those obtained in near-sea-level control animals (low-altitude group). In response to hypercapnia (arterial PCO2 = 63 +/- 2 torr vs 42 +/- 1 torr baseline), high-altitude fetuses showed similar increases in LD-CBF, cortical tPO(2), and sagittal sinus (HbO(2)) as compared with those responses seen in the fetus at low attitude. Nonetheless, these fetuses showed a significantly smaller decrease in cerebral fractional O-2 extraction compared to low-altitude fetuses. In response to hypercapnia in high-altitude, acclimatized, long-term hypoxic fetal sheep) the response of CBF and cerebral oxygenation did not differ significantly from that of low-altitude controls.