The present study was performed to determine whether positron emission tomography performed after intravenous injection of 11C-palmitate permits detection and characterization of congestive cardiomyopathy. Positron emission tomography was performed after the intravenous injection of 11C-palmitate in 13 normal subjects, 17 patients with congestive cardiomyopathy, and six patients with initial transmural myocardial infarction (defined electrocardtographically). Regionally depressed accumulation of 11C-palmitate was assessed, characterized, and quantified in seven parallel transaxial reconstructions in each patient. Normal subjects exhibited homogeneous accumulation of 11C-palmitate within the left ventricular myocardium, with smooth transitions in regional content of radioactivity. Patients with cardiomyopathy exhibited marked spatial heterogeneity of the accumulation of palmitate throughout the myocardium, easily distinguishable from that in normal subjects and distinct from that observed in patients with transmural infarction, in whom discrete regions of depressed accumulation of palmitate were observed with residual viable myocardium accumulating palmitate homogeneously. Patients with cardiomyopathy exhibited a larger number of discrete noncontiguous regions of accumulation of palmitate within the myocardium than either control subjects or patients with transmural infarction (17.4 ± 0.6 [SEM] versus 11.8 ± 0.7 versus 10.3 ± 0.6, p < 0.005). Similarly, regions of accumulation of palmitate were irregularly shaped in patients with cardiomyopathy, with a longer normalized perimeter than either control subjects or patients with transmural infarction (2.0 ± 0.05 versus 1.8 ± 0.06 versus 1.9 ± 0.09, p < 0.05). Regional abnormalities of the accumulation of 11C-palmitate could not be explained by regional differences in left ventricular wall motion or myocardial perfusion. Thus, marked heterogeneity of regional myocardial accumulation of 11C-palmitate is detectable and quantifiable in patients with congestive cardiomyopathy by positron emission tomography and may be particularly valuable for early detection and characterization of cardiomyopathy.