Along with hibernating myocardium, infarct size is a critical term in the progression of left ventricular remodelling and congestive heart failure. Both infarcted and hibernating myocardium determine changes in remote non-ischaemic tissue. This study was designed to test the accuracy of a new technique to quantify infarct size using positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose (FDG). Studies were carried out in (a) nine pigs with acute myocardial infarction (two sham-operated), produced by a 90-min occlusion of the circumflex coronary artery followed by a 4-h reperfusion, and (b) humans (six patients with ischaemic cardiomyopathy awaiting cardiac transplantation and five normal volunteers). In both animals and patients, myocardial FDG uptake was measured by PET during hyperinsulinaemic-euglycaemic clamp. Infarct size was quantified by an absolute threshold of tracer uptake obtained from the parametric (voxel-by-voxel) image of the metabolic rate of FDG. PET infarct size estimates were compared with independent ex vivo planimetric measurements of the explanted swine and patient hearts (at transplantation) after staining with triphenyltetrazolium chloride. There was good agreement between the planimetric and PET infarct size estimates both in pigs (n=9; r=0.96, v=0.94x+0.64, SEE=0.10, P<0.0001) and in humans (n=11; r=0.94, y=0.72x+2.93, SEE=0.09, P<0.0001). This study demonstrates the feasibility and accuracy of this PET method in estimating infarct size both in a model of reperfused acute myocardial infarction and in chronic ischaemic cardiomyopathy, although larger studies are needed to confirm these findings.