Chronic exposure to hypoxia is associated with muscle atrophy (i.e. reduction in muscle fiber cross-sectional area), reduced oxidative capacity and capillary growth. It is controversial whether these changes are muscle and fiber type specific. We hypothesized that different regions of the same muscle would also respond differently to chronic hypoxia. To investigate this we compared the deep (oxidative) and superficial (glycolytic) region of the plantaris muscle of 8 male rats exposed to 4 weeks hypobaric hypoxia (410 mm Hg; PO₂ 11.5 kPa) with those of 9 normoxic rats. The hematocrit was higher in chronic hypoxic than control rats (59 vs. 50%; P<0.001). Using histochemistry, we observed a 10% fiber atrophy (P<0.05) in both regions of the muscle, but no shift in fiber type composition and myoglobin concentration of the fibers. In hypoxic rats, the succinate dehydrogenase (SDH)-activity was elevated in fibers of each type in the superficial (25%, P<0.05), but not in the deep region, while in the deep, but not the superficial region, the number of capillaries supplying a fiber was elevated (14%, P<0.05). Model calculations showed that the region-specific alterations in fiber size, SDH-activity and capillary supply to a fiber prevented the occurrence of anoxic areas in the deep region, but not in the superficial region. Inclusion of reported acclimatization-induced increases in mean capillary oxygen pressure (attenuated the development of anoxic tissue areas in the superficial region of the muscle. We conclude that the determinants of tissue oxygenation show region specific adaptations, resulting in a marked differential effect on tissue oxygen tension.