Alterations in skeletal muscle structure were investigated in 6 male subjects who underwent 40 days of progressive decompression in a hypobaric chamber simulating an ascent to the summit of Mount Everest. Needle biopsies were obtained from vastus lateralis of 5 subjects before and immediately after confinement in the chamber, and were examined for various structural and ultrastructural parameters. In addition, total muscle area was calculated in 6 subjects from CT scans of the thighs and upper arms. Muscle area at these sites was found to decrease significantly (by 13 and 15%) as a result of the hypobaric confinement. This was substantiated by significant (25%) decreases in cross sectional fibre areas of the Type I fibres and 26% decreases (non significant) in Type II fibre area. Capillary to fibre ratios remained unchanged following hypoxia as did capillary density although there was a trend (non significant) towards an increase in capillary density. There were no significant increases in mitochondrial volume density or other morphometric parameters. These data indicate that chronic, severe hypoxia on its own does not result in an increase in absolute muscle capillary number or a de novo synthesis of mitochondria. The trends toward an increase in capillary density and mitochondrial volume density were interpreted as being secondary occurrences in response to the pronounced muscle atrophy which occurred.