Human tolerance to chronic severe hypoxia has been elucidated by two recent high altitude studies: the 1981 American Medical Research Expedition to Everest, and Operation Everest II, a 40-day low pressure chamber-simulated ascent of Everest. The severe oxygen deprivation of extreme altitudes can only be tolerated because of an enormous increase in ventilation which defends the alveolar Po2 against the reduced inspired value. Nevertheless the arterial Po2 on the Everest summit is less than 30 mmHg. The hyperventilation results in a very low arterial Pco2 which causes severe respiratory alkalosis. This has the advantage of increasing the oxygen affinity of hemoglobin and accelerating the oxygen loading by the pulmonary capillary under diffusion-limited conditions. Cardiac function is astonishingly well maintained up to extreme altitudes. The relationship between cardiac output and work rate is the same as at sea level, and there is evidence that myocardial contractility is well preserved in spite of the extreme hypoxemia. However, there is impairment of central nervous system function at high altitude which persists following return to sea level. Significant abnormalities of motor coordination persisted for more than 12 months in most members of the Everest expedition. There is evidence that the climbers who ventilate most at high altitude have the most central nervous system impairment, presumably because of the more severe cerebral vasoconstriction.