Residence at extreme altitude results in pronounced reductions in muscle mass and the cross-sectional area of the slow and fast twitch fibre types. The reductions in muscle contractile proteins appear not to be accompanied by significant alterations in the proportion of the major fibre types and consequently in the myosin heavy chain isozymes. Acclimatization to extreme altitude is also accompanied by a marked reduction in mitochondrial potential that occurs regardless of activity status. At least during mountaineering expeditions, the maximal activity of cytosolic enzymes involved in anaerobic function appear to be unaffected. In contrast, extreme hypobaric hypoxia with low exercise appears to result in loss of the activities of cytosolic enzymes. The attenuation of glycolysis during exercise accompanying acclimatization does not appear to be due to adaptations in fibre size, capillarization or mitochondrial potential. Rather, evidence from both acclimatization and training at sea level suggests that a depressed blood epinephrine concentration is involved.