To determine whether positron emission tomography (PET) after the combined administration of 11C-palmitate intravenously to image myocardium and 11CO by inhalation to image the cardiac blood pool with 11CO-hemoglobin provides quantitative delineation of the locus and extent of myocardial infarction, 28 patients with suspected myocardial infarction were studied. Twenty-one patients had electrocardiographically documented transmural infarction and in seven, the diagnosis of infarction was ultimately excluded based on enzymatic and electrocardiographic criteria. To assess reproducibility, four patients were studied on two occasions 1 month apart. Inferior and apical infarcts were readily localized with sagittal and coronal as opposed to transaxial reconstructions. Complete electrocardiographic and tomographic concordance was observed for the locus of all transmural infarcts. Reproducibility of tomographic estimates was within 10%. Tomographic estimation of the extent of infarction with 11C-palmitate in a subset of patients in whom right ventricular contributions to overall enzyme release could be excluded was facilitated by delineation of the endocardial border with the 11CO-hemoglobin cardiac blood pool image in the same plane. The correlation between enzymatic (serial plasma MB-CK method) and tomographic estimates of infarct size was close (r= 0.92). Thus, as has been shown in experimental animals, PET with 11C-palmitate permits quantification and localization of myocardial infarcts in patients.