Thallium-201 scintigraphic defects are observed in most patients with ischemic cardiomyopathy and also can be found in idiopathic dilated cardiomyopathy. To determine the ability of qualitative and quantitative perfusion parameters to differentiate these entities, thallium-201 exercise testing was performed in 51 patients with coronary arteriography referred for evaluation of severe congestive heart failure. All patients had a left ventricular ejection fraction < 35%. Thirty-one ischemic patients had coronary stenosis > 70% in > or = 1 artery, and 20 idiopathic patients had no coronary stenosis or identifiable cause of heart disease. Similar exercise capacity, ejection fraction and sex distribution were found in both groups. Ischemic patients more often had severe perfusion defects (97 vs 25%; p = 0.00001), large perfusion defects involving > or = 40% of the left ventricular contour (100 vs 80%; p = 0.01), and increased thallium-201 lung uptake (94 vs 65%, p = 0.01). Large severe defects were present in 90% of ischemic and only 5% of idiopathic patients. On quantitative analysis, the area of the thallium-201 curve less than normal was greater in ischemic than idiopathic patients (14.8 +/- 9.5% vs 3.3 +/- 2.8%; p = 0.001). The degree and severity of redistribution were similar in both groups. Multivariate analysis identified the qualitative parameters of increased thallium-201 lung uptake, severe defects and large severe defects as the only independent predictors of the presence of ischemic disease. The presence of large severe defects had a 97% predictive value for ischemic cardiomyopathy. The absence of severe defects had a 94% predictive value for idiopathic dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)