In ischemic cardiomyopathy (CM) fibrosis replaces large segments of myocardium, but in idiopathic congestive CM the myocardium contains only small foci of fibrosis or is morphologically normal. As coronary disease and myocardial infarction may be clinically silent, it is not always possible to distinguish ischemic from idiopathic congestive CM during life without cardiac catheterization. To determine whether noninvasive methods, thallium 201 myocardial (Tl) imaging and technetium 99m gated cardiac blood pool scans (GCBPS), could separate the entities, we evaluated radioisotope images of the heart in 13 patients with ischemic, and eight patients with idiopathic congestive CM, and 14 patients with normal hearts. Diagnosis was setablished by cardiac catherterization and/or autopsy in each of the 35 patients. The 14 normals could be readily distinguished from CM, and ischemic could be distinguished from idiopathic dilated CM in 20 of 21 patients. All patients with myocardiopathy showed hypokinetic and dilated left ventricles, but right ventricular dilatation was evident mainly in those with idiopathic CM. Tl images in the ischemic type had defects of greater than 40% of image circumference which corresponded to segmental wall motion abnormalities on GCBPS, whereas those with the idiopathic congestive form were homogeneous or had defects of less than 20% of image circumference. Autopsy studies in 7 of 35 patients correlated Tl defects of greater than 20% of circumference with transmural myocardial fibrosis.