Twenty-one dogs were studied under conditions of normal oxygenation and hypoxia with the microsphere distribution method to determine the effect of arterial oxygen saturation on the regional distribution of cardiac output. The dogs were anesthetized and artifically ventilated. Cannulas were placed in the left ventricle to administer microspheres and in a peripheral artery to determine cardiac output. Each dog received two microsphere injections: (1) while normally oxygenated (room air), and (2) under hypoxia (10% oxygen-90% nitrogen in 10 dogs and 5% oxygen-95% nitrogen in 11 dogs). Absolute cardiac output increased from 87 +/- 15 ml/min per kg to 101 +/- 14 ml/min per kg during mild hypoxia (10% oxygen) (P less than 0.05), and from 73 +/- 17 ml/min per kg to 120 +/- 24 ml/min per kg during severe hypoxia (5% oxygen) (P less than 0.01). Absolute blood flows increased to all organs except skin and muscle during hypoxia, although there were decreases in the fractional distribution of cardiac output to the splanchnic bed and kidney. Striking changes were found in coronary, hepatic, and cerebral circulation, and the organ with, greatest response to hypoxia was the heart, with increased coronary flow of 37% and 285% during exposure to 10% and 5% oxygen, respectively. Hence, low oxygen levels in blood cause redistribution of cardiac output and arterial content plays an important role in blood flow regulation.