A physiologic means of measuring the distribution of cardiac output and regional myocardial blood flow has been developed that uses human albumin microspheres labeled with carbon-11 (11C) and external detection with positron emission tomography. Ten patients with previous myocardial infarction were studied to investigate the level of blood flow in normal and infarcted segments of the heart. After diagnostic catheterization, 4 to 6 mCi of11C on 2 to 3 million sterile microspheres (15 to 20 μm) were mixed and injected into the apex of the left ventricle during timed withdrawal of arterial blood to obtain reference flow values. Regional activity in brain, heart, lungs, liver, spleen, and kidneys was measured tomographically. Blood flow was calculated based on the relationship between total activity in a reference flow and tissue activity in tomograms of each organ (ml/min/100 g). No adverse effects were noted after injection of the microspheres. Successive myocardial tomograms showed no loss of activity. There were no significant differences in flow values in matched regions of paired organs. Mean cerebral flow was 52.4 ± 10.0 ml/min/100 g in the frontal lobes, 54.4 ± 8.8 in the temporal lobes, 67.6 ± 8.2 in the occipital lobes, and 53.0 ± 9.4 in the basal ganglia. Flow was 16.0 ± 8.4 ml/min/100 g (range 0 to 40.0) in the center of infarcted myocardium and 82.0 ± 32.0 in the remote segments. This method meets most of the demands for use of microspheres to measure tissue blood flow. The wide range of flow values in infarcted myocardium may be a function of infarct size, spatial resolution, or pathologic evidence of islands of viable tissue. Patients with angina had high flow values in the infarcted segment, whereas those with heart failure had significantly lower values. Surviving myocardium in the region of the infarct may need to be considered if patients complain of angina, particularly when treatment is aimed at preserving ventricular function.