The biochemical, histochemical, and structural changes induced by endurance training and long-term exposure to high altitude were studied in the diaphragm muscle of rats exposed to simulated altitude (HA: n = 16; Pb = 62 kPa, 463 Torr; 4000 m) and compared to animals maintained at sea-level (SL: n = 16). Half of the animals in each group were trained (T) by swimming for 12 weeks, the other half were kept sedentary (S). Except for a small decrease in type I fibres in the HA-S group (-7%, P < 0.05), in favour of type IIab and type IIb fibres, neither high-altitude exposure nor endurance training had an overall affect on fibre type distribution. The mean fibre cross-sectional area was found to be unaffected by altitude and/or chronic exercise. Capillary density was shown to be increased by both high-altitude exposure (P < 0.02) and training (P < 0.001), whereas capillary growth, estimated by the capillary/fibre ratio, was unaffected in both cases. Following endurance training, a modest increase in citrate synthase was shown to occur to the same extent in the HA-T and SL-T groups (+15% and +16% respectively, NS). Hexokinase increased following training (P < 0.05) and high-altitude exposure (P < 0.001). In normoxic and hypoxic animals, endurance training enhanced the ratio of the heart-specific lactate dehydrogenase isozyme LDH1 to total LDH activity (+59%, P < 0.01; +92%, P < 0.05 respectively). It may be hypothesized that the increased glucose phosphorylation capacity observed in diaphragm muscle contributes to the reduction of glycogen utilization during exercise.