Three adult mongrel dogs (2 males and 1 female) native to Denver [Colorado, USA] were studied before and after a 3 wk exposure to a simulated altitude of about 4880 m during which time they received food and water ad lib. Because the dogs were trained to run on a treadmill, the sternothyroideous muscle was examined in order to minimize the possible effects of exercise on the skeletal muscle. Before and after exposure to high altitude, a portion of this muscle was studied histologically. In Denver, at 1610 m above sea level, the average capillary density in cross sections of skeletal muscle was 624 capillaries/mm2. Approximately a 2-fold increase in the number of capillaries was found after 3 wk at 435 mmHg. As a consequence and because capillary diameter remained unchanged, the capillary volume density, i.e., the relative volume occupied by capillaries in a unit volume of tissue, and the relative surface area of capillaries per unit volume of tissue also doubled. A significant decrease in the average diameter of the muscle fibers from 65 to 46 .mu.m was found after 3 wk at 435 mmHg, but the relative muscle fiber volume per unit volume of tissue remained the same. The relative surface area density for muscle fibers increased from 85.7 .mu.m2/1000 .mu.m3 at 435 mmHg to 111.0 .mu.m2/1000 .mu.m3 at 435 mmHg. The number of capillaries per muscle fibers did not change upon exposure to hypoxia. The reduction in fiber size that occurs upon exposure to simulated altitude is advantageous because in these conditions, the capillary blood has a low PO2 [O2 tension] but the metabolic rate is essentially the same. The arterial PO2 in these dogs decreased from an average of 72 mmHg in Denver to 47 mmHg at 4880 m. Due to the compensatory hemodynamic and hematologic changes the P.hivin.vO2 fell only from about 37 to about 32 mmHg so that the average capillary PO2 calculated using Barcroft''s formula fell from 54 to 38 mmHg. Under these conditions, and if the diffusion constant and the metabolic activity of the muscle do not change, it is estimated that the PO2 in the center of the muscle fiber in hypoxia is even higher than that found at sea level, due to the decreased size of the muscle fiber.