Study objectives: In patients with terminal lung disease who were exercising, we assessed whether improved arterial O-2 saturation with an increased fraction of inspired oxygen (FIO2) affects cerebral oxygenation. Design: Randomized, crossover. Patients and methods: The cerebral changes in oxyhemoglobin (DeltaHbO(2)) and changes in deoxyhemoglobin (DeltaHb) levels were evaluated using near-infrared spectrophotometry and the middle cerebral artery (MCA) mean velocity (Vmean) was determined by transcranial Doppler ultrasonography in 13 patients with terminal lung disease (New York Heart Association class III-IV). Patients were allocated to an FIO2 of either 0.21 or 0.35 during incremental exercise with 15 min between trials. Results: Peak exercise intensity (mean [ SE], 26 4 W) reduced the arterial O-2 pressure (at rest, 64 +/- 3 mm Hg; during exercise, 56 3 mm Hg) and the arterial oxygen saturation (SaO(2)) [at rest, 92 +/- 2%; 87 +/- 2%; p < 0.05], while the arterial CO2 pressure was not significantly affected. The MCA Vmean increased from 49 5 to 63 7 ends (p < 0.05) as did the AM, while the DeltaHbO(2) remained unaffected by exercise. With an elevated FIO2, the SaO(2) level (at rest, 95.8 +/- 0.7%; during exercise, 96.0 +/- 1.0%) and arterial O-2 pressure (at rest, 102 +/- 11 mm Hg; during exercise, 100 +/- 8 mm Hg) were not significantly affected by exercise, and the levels of blood oxygenation remained higher than the values established at normoxia (p < 0.05). The MCA Vmean increased to a level similar to that achieved during control exercise (ie, to 70 +/- 11 cm/s). In contrast to control exercise, DeltaHb decreased while DeltaHbO(2) increased during exercise with 35% O-2 (P < 0.05) Conclusion: An O-2-enriched atmosphere enabled patients with terminal lung disease to maintain arterial O-2 saturation during exercise. An exercise-induced increase in cerebral perfusion was not affected by hyperoxia, whereby the enhanced availability of oxygenated hemoglobin increases cerebral oxygenation. The clinical implication of the study is that during physical activity patients,with terminal lung disease are recommended to use an elevated FIO2 to protect cerebral oxygenation.