The present study was performed to determine whether positron emission tomography (PET) performed after i.v. 11C-palmitate permits detection and characterization of nontransmural myocardial infarction. PET was performed after the i.v. injection of 11C-palmitate in 10 normal subjects, 24 patients with initial nontransmural myocardial infarction (defined electrocardiographically), and 22 patients with transmural infarction. Depressed accumulation of 11C-palmitate was detected with sagittal, coronal and transverse reconstructions, and quantified based on 14 contiguous transaxial reconstructions. Defects with homogeneously intense depression of accumulation of tracer were detected in all 22 patients with transmural infarction (100%). Abnormalities of the distribution of 11C-palmitate in the myocardium were detected in 23 patients with nontransmural infarction (96%). Thallium scintigrams were abnormal in only 11 of 18 patients with transmural infarction (61%). Tomographically estimated infarct size was greater among patients with transmural infarction (50.4 ± 7.8 PET-g-Eq/m2 [± SEM]) compared with those with nontransmural infarction (19 ± 4 PET-g-Eq, P < 0.01. Residual accumulation of 11C-palmitate within regions of infarction was more intensely depressed among patients with transmural compared to nontransmural infarction (33 ± 1 vs 39 ± 1% maximal myocardial radioactivity, p <0.01). Thus, PET and metabolic imaging with 11C-palmitate is a sensitive means of detecting, quantifying and characterizing nontransmural and transmural myocardial infarction.