This study examined the value of resting thallium-201 imaging in differentiating patients with primary cardiomyopathy from those with ischemic cardiomyopathy. There were 15 patients with primary cardiomyopathy (group I); 20 with chronic CAD (group II); and 25 with acute Q wave myocardial infarction (group III). All patients had LVEF less than or equal to 35%. The thallium score was less than 50 (maximum 60) in one patient (7%) in group I, in 17 patients (85%) in group II, and in 25 patients (100%) in group III (p less than 0.0001, I vs II and III). The number of normal segments was 11.4 +/- 4.9 in group I, 6.9 +/- 2.9 in group II, and 7.0 +/- 2.2 in group III (p less than 0.0001, I vs II, III). Reversible defects were present in three patients in group II, three in group III, and none in group I. Abnormal right ventricular thallium uptake was observed in 27% of patients in group I, 25% in group II, and 40% in group III (p = NS). Abnormal lung thallium uptake was observed in 33% in group I, 20% in group II, and 20% in group III (p = NS). Thus, rest thallium imaging is useful in separating patients with primary cardiomyopathy from those with ischemic cardiomyopathy.