Regional cerebral oxygenation (rSO2) and peripheral oxygen saturation (SpO2) have been studied in subjects inside a portable hyperbaric chamber at altitude during pressurization. The effects of the accumulation of carbon dioxide within the chamber on rSO2 and SpO2 have also been investigated. Three studies of cerebral regional oxygenation were undertaken, using near-IR spectroscopy, in subjects who had ascended to 3475 m in the Alps, 4680 m in the Andes or 5005 m in the Himalayas. At 3475 m and 5005 m the effects of the removal of inspired carbon dioxide by a soda lime scavenger were also studied. On pressurization of the chamber to 19.95 kPa, inspired carbon dioxide rose within the chamber from 0.03% (0.06 kPa) ambient to over 1% (1.3 kPa). At 5005 m, SpO2 rose from a baseline of 79.5% (S.D. 4.5%) to 95.9% (2.0%) (P<0.0001), and cerebral rSO2 rose from 64.6% (3.4%) to 69.4% (3.6%) (P<0.0001). The introduction of a soda lime CO2 scavenger into the breathing circuit resulted in a drop in SpO2 from 95.9% (2.03%) to 93.6% (2.07%) (P<0.001) and a fall in rSO2 from 69.4% (3.64%) to 68.5% (3.5%) (P<0.01). Chamber pressure was maintained throughout at 19.95 kPa. Similar changes were seen at the other altitudes. Cerebral rSO2 increased rapidly following pressurization at all three altitudes. Scavenging of inspired carbon dioxide was associated with a significant fall in cerebral rSO2 and SpO2, and we estimate that the contribution of carbon dioxide may account for up to one-third of the beneficial effect of the portable hyperbaric chamber.