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 m; 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 PO(2) (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 PCO(2) = 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 altitude. 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.