We studied the cardiorespiratory effects of acute hypercapnia in 10 unanesthetized sheep. After a 15-min exposure to either 7.3 or 10% CO2 in air, we measured arterial blood gases, minute ventilation (V̇E), O2 consumption (V̇O2), cardiac output (Q̇), heart rate (HR), an index of left ventricular contractility [(dP/dt)/P], and vascular pressures. In addition, regional flows to all major organs were determined by injecting 15-μm radiolabeled microspheres into the left heart. Exposure to 7.3% CO2 (arterial CO2 partial pressure, PaCO2 58 Torr) resulted in increased V̇E, (dP/dt)/P, and higher blood flows to the brain and respiratory muscles. All other variables remained unchanged. Exposure to 10% CO2 (PaCO2 75 Torr) resulted in a further augmentation of V̇E and a 48% increase in Q̇, which was associated with a tachycardia, a decrease in systemic vascular resistance, and an increase in V̇O2. Coronary and respiratory muscle flows increased, but all other variables remained unchanged. Thus the hemodynamic effects of hypercapnia are not related linearly to the level of PaCO2.