It is a strange coincidence that the highest point on Earth is very close to the limit of human tolerance to hypoxia. The physiological changes that allow humans to reach these extreme altitudes involve enormous alterations of their normal state. It is useful to contrast this response with two others to high altitude. One is acclimatization that allows lowlanders to ascend to altitudes of up to 5000 m and remain there for an indefinite period. The other is evolutionary adaptation which allows highlanders to live continuously over generations at altitudes up to 5000 m. These two responses enable humans to survive for an indefinite period at high altitude. By contrast, the changes that allow ascent to extreme altitudes are not compatible with an extended stay because of a poorly-understood process called high-altitude deterioration. The most important physiological response to extreme altitude is extreme hyperventilation which, on the summit of Mt. Everest, drives the alveolar P(CO(2)) down to 7-8 mmHg. This is associated with a marked respiratory alkalosis with an arterial pH exceeding 7.7. Interestingly this alkalosis increases the oxygen affinity of hemoglobin, a response which the successful climber shares with many other animals in oxygen-deprived environments. The arterial P(O(2)) on the Everest summit is only about 30 mmHg and falls on exercise because of diffusion limitation of oxygen across the blood-gas barrier. Maximal oxygen consumption on the summit is just over 1 liter.min(-1). Anaerobic metabolism as measured by blood lactate levels is paradoxically reduced at extreme altitudes.