To examine the effects of isoflurane on systemic distribution of cardiac output, organ/tissue blood flow was measured in 11 isocapnic pigs using 15-μm diameter radionuclide-labeled microspheres injected into the left atrium. Measurements were made on each pig during five of the following six conditions: awake (control); 1.0 MAC (1.45% end-tidal) isoflurane anesthesia; 1.5 MAC (2.18% end-tidal) isoflurane anesthesia; 0.95% end-tidal isoflurane and 50% N2O anesthesia equivalent to 1.0 MAC; 1.68% end-tidal isoflurane and 50% N2O anesthesia equivalent to 1.5 MAC; and 50% N2O administration. The order of anesthetized steps was randomized. A period of 60 min was interposed between anesthetized steps to allow pigs to recover towards control values. Mean aortic pressure decreased in a dose-related manner during isoflurane anesthesia, whereas cardiac output decreased only during 1.5 MAC isoflurane anesthesia and heart rate remained unchanged. The addition of N2O attenuated the hypotensive effects of isoflurane and cardiac output was maintained near control values because of increased heart rate. Brain blood flow increased in a dose-dependent manner with isoflurane anesthesia, but myocardial blood flow exhibited a dose-related decrease. The addition of 50% N2O to maintain the same total MAC anesthesia resulted in a larger increase in brain blood flow especially at 1.5 MAC, while myocardial blood flow was maintained near control value. Rate—pressure product and myocardial blood flow at 1.5 MAC anesthesia were higher when N2O was used with isoflurane. While blood flow and fraction of cardiac output going to the adrenal glands were unaltered during isoflurane-N2O anesthesia, blood flow increased at 1.5 MAC isoflurane anesthesia. Splenic blood flow and splenic fraction of cardiac output were increased at both MAC levels of isoflurane as well as isoflurane-N2O anesthesia whereas blood flow to the stomach, small intestine, diaphragm, skeletal muscle, and adipose tissue decreased from control values. Renal, hepatic arterial, and cutaneous bood flow remained unaltered. Fifty percent N2O in the presence of a residual end-tidal isoflurane concentration of 0.20% caused heart rate to increase from control levels, while cardiac output and mean aortic pressure were unaltered. Brain blood flow increased by 27% above control values, but perfusion in the myocardium, adrenal glands, spleen, kidneys, liver, and skin was unchanged. Stomach, small intestine, skeletal muscle, and diaphragm blood flows decreased from control values, whereas perfusion of adipose tissue increased.