Positron-emission computed tomography (PCT) is a new means of studying regional myocardial metabolism. This new device permits quantitative, cross-sectional imaging of the tissue concentrations of positron-emitting tracers of blood flow and metabolism in the myocardium. To examine the potential value of PCT for evaluating regional alterations in myocardial metabolism, acute myocardial ischemia was induced by rapid atrial pacing in open-chest dogs with partial coronary stenoses. Regional myocardial glucose uptake and utilization of free fatty acids were examined with the glucose analog F-18 2-fluoro-2-deoxyglucose (FDG) and C-11-labeled palmitic acid. Myocardial blood flow was evaluated with N-13 ammonia. In the ischemic segment, uptake of C-11 palmitic acid was reduced in proportion to blood flow and its rate of clearance as an index of beta oxidation was delayed. There was a relative or absolute increase in FDG uptake (depending on the uptake of FDG in the normal myocardium). Similar observations were made in patients with ischemic heart disease and anginal symptoms at the time study. The observed alterations in the regional distribution of positron-emitting tracers of metabolic substrates in ischemic myocardium are in agreement with previously reported animal experimental studies in which a fall in free fatty acid utilization associated with an increase in glycolytic flux was observed. These studies indicate that metabolic alterations associated with acute myocardial ischemia observed previously in destructive animal experiments do indeed occur in humans and can now be demonstrated noninvasively in humans by PCT.