The effects of inspiring low O2 or high CO2, or low-O2-high-CO2 gas mixtures on tissue perfusion and tissue Po2 of brain and muscle were studied in 76 anesthetized rats. Under control conditions, relative tissue Po2 of cerebral white matter measured polarographically averaged 16.4 mmHg and 18.7 mmHg in the biceps brachii. With low-O2 gas mixtures, tissue Po2 declined in both brain and muscle, but more in muscle. Tissue Po2 increased under high-CO2 conditions, with the brain increasing to a greater extent. Control cerebral cortex tissue perfusion averaged 23.5 ml/min per 100 g and muscle was 18.3 ml/min per 100 g measured by H2 clearance. Brain perfusion increased under all experimental conditions. Muscle perfusion did not change with low O2 alone, but increased with low-O2-high-CO2 or high-CO2 gas mixtures. Brain perfusion increased under all conditions significantly more than muscle. The brain appeared better protected compared to skeletal muscle in terms of tissue Po2 and perfusion under the stress of hypoxia and hypoxic-hypercapnia. The effects of hypercapnia are also greater on the brain.