Positron emission tomography with 15O-labeled water (H215O) can be used to delineate abnormal regional myocardial blood flow in experimental animals. To determine the feasibility of this method in humans, we studied 33 subjects (9 normal volunteers and 24 patients with angiographically documented coronary artery disease) at rest and after myocardial hyperemia induced with intravenous infusion of dipyridamole. At rest, the myocardial region demonstrating the lowest relative H215O activity exhibited 71 ± 8% of activity in the region with peak activity in control subjects and 62 ± 17% in patients (p = NS). After the dipyridamole infusion, differences between the two groups were accentuated. In control subjects, activity in the region with lowest relative radioactivity averaged 77 ± 5% of that in the region with peak activity. In patients, it averaged 55 ± 22% of activity in the region with peak activity (p < 0.01). Results in patients with ischemia with or without a history of remote myocardial infarction were not significantly different. In 22 of the 24 patients, the region with lowest relative perfusion corresponded anatomically to the region of myocardium distal to a stenosis. Thus, delineation of regional myocardial perfusion in patients with coronary artery disease is possible with positron emission tomography and H215O. Further studies will be necessary to prospectively determine sensitivity and specificity.