We have studied the effects of severe acute hypoxemia (PaO2 = 25 torr) on cardiac output (Q), heart rate (HR), left ventricular contractility ((dP/dt)max/P), intravascular pressures and blood flow to the heart, brain, abdominal viscera, skin and respiratory and non-respiratory muscles in twelve conscious ewes that breathed a mixture of 8% O2 and 92% N2 for 20 min. Q, HR, (dP/dt)max/P) and systemic and pulmonary arterial pressures increased. Total peripheral resistance decreased while pulmonary vascular resistance remained unchanged. Coronary, cerebral, respiratory and nonrespiratory muscle and adrenal flows increased, in association with a decrease in regional vascular resistances, while the flows to the kidney and other abdominal viscera remained unchanged. The concentration of total plasma catecholamines doubled, indicating that the sympathetic nervous system plays a major role in the hemodynamic response to this level of hypoxia. Increased oxygen delivery to the heart (31%) and respiratory muscles (44%) were brought about by increases in both the magnitude and the redistribution of Q, the latter being the more important of the two mechanisms. In contrast, both mechanisms contributed equally to the amount of oxygen delivered to the brain and nonrespiratory muscles. We concluded that in acute hypoxemia, both the increase in Q and its regional redistribution contribute to the delivery of oxygen to the various tissues.