At cardiac catheterization, the effect of isoproterenol on coronary blood flow was compared in six patients with normal coronary arteries and normal left ventricular function, and eight patients with angiographically defined coronary lesions. Coronary blood flow was measured by selective coronary artery injection of xenon-133 and external monitoring of disappearance curves with a dual probe, digital scintillation counter. Resting values did not differ in the two groups. In the normal group isoproterenol increased mean coronary blood flow 93 ml/100 g/min (152%) and cardiac output 2.3 liters/min (42%); coronary resistance/100 g decreased 60 ± 4% (SEM), while total peripheral resistance decreased 29 ± 4%. In the coronary disease group coronary blood flow increased 20 ml/100 g/min (33%) and cardiac output increased 2.8 liters/min (62%); coronary resistance decreased 26 ± 9% and total peripheral resistance decreased 37 ± 4%. In all normal patients the percent increase in coronary blood flow markedly exceeded the percent increase in cardiac output and the percent fall in coronary resistance markedly exceeded the percent fall in total peripheral resistance. In six of the eight patients with coronary lesions the percent increase in coronary blood flow was less than the percent increase in cardiac output and the fall in coronary resistance was less than the fall in total peripheral resistance. Thus measurement of coronary blood flow, cardiac output, and aortic pressure before and during isoproterenol infusion may permit differentiation of those subjects with physiologically significant coronary obstructions.