OBJECTIVE We tested the hypothesis that O2 administration to the mother would increase arterial O2 tension (PaO2) and cortical tissue O2 tension (tPO2) in both the normoxic control fetus and that acclimatized to high altitude, and that this effect might be greater in the high altitude fetus than that at sea level. METHODS Pregnant ewes were divided into either low-altitude group or high-altitude group (3820 m; maintained from day 30 of gestation to near-term, term = 145 days; n = 6 each). In near-term fetuses we instrumented the cerebral cortex with tissue PO2-laser Doppler flow probes, and placed arterial catheters. With the ewe breathing either air or 50% O2, we measured fetal arterial and brain tissue PO2 and cerebral blood flow (CBF). RESULTS In response to maternal O2 administration, in both low- and high-altitude fetuses, PaO2, O2 content, and brain tissue PO2 increased significantly. Nonetheless, the fetuses at high altitude showed significantly greater increase in both PaO2 and cerebral tPO2, than that seen in fetuses at low altitude. In neither group was there a change in CBF or cerebral metabolic rate for O2. CONCLUSIONS Maternal O2 administration significantly increased PaO2 and cerebral tPO2 of the fetus both at low altitude and at high altitude, with this increase being greater in the high altitude animals. We suggest that maternal O2 administration can have an important effect in ameliorating nonreassuring fetal status, and perhaps be of value in instances of mothers who smoke heavily or with cardiopulmonary disease.