Cerebral oxygenation is likely to be of critical importance in determining function at high altitude. The present study has used the technique of near-IR spectroscopy to monitor changes in cerebral regional oxygenation in response to inhaled carbon dioxide, hyperventilation and supplementary oxygen on ascent to 4680 m over 3 days. At sea level, inhaled CO2 resulted in a significant rise in cerebral regional oxygenation [from mean 69.6% (S.D. 2.4% to 71.1±2.3%; means±S.D.; P < 0.001). At 4680 m, CO2 increased regional cerebral oxygenation (63.8±2.5% to 65.9±2.2%; P < 0.001) and also increased peripheral oxygen saturation (75.1±6.1% to 83.6±4.0%; P < 0.001). Voluntary hyperventilation resulted in improved peripheral oxygen saturation at 2770 m, 3650 m and 4680 m, whereas cerebral regional oxygenation was reduced at sea level and at 2770 m, unchanged at 3650 m and increased at 4680 m. Supplementary oxygen (6 1itres/min) at 4680 m resulted in greater improvements in peripheral oxygen saturation (76.7±7.9% to 98.1±1.5%; P < 0.001) and cerebral regional oxygenation (64.6±3.3% to 70.6±2.9%; P < 0.001) than were found with CO2 or hyperventilation. We conclude that attempts to increase CO2 inhalation or ventilation at high altitude are likely to be beneficial for cerebral oxygenation in the short term.