To determine if imaging of blood flow (using 201Tl) and fatty acid (using 123-I-BMIPP) with SPECT can distinguish cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy, 24 patients with severe left ventricular dysfunction were evaluated. The origin of left ventricular dysfunction had been previously determined by coronary angiography to be ischemic (9 patients) or nonischemic (15 patients). Images were visually analyzed by three observers on a graded scale (score 0; normal, 1; mild uptake reduction, 2; severe uptake reduction, and 3; defect) in 20 left ventricular segments revealed higher defect score in ICM compared with NCM for 123I-BMIPP (35.5 +/- 14.4 versus 14.1 +/- 9.3, p <0.0005) and 201Tl (27.6 +/- 14.6 versus 12.1 +/- 7.4, p <0.005). The defect score/segment ratio also revealed higher value in ICM compared with NCM for 123I-BMIPP (2.25 +/- 0.52 versus 1.36 +/- 0.36, p <0.0001) and 201Tl (1.92 +/- 0.51 versus 1.24 +/- 0.42, p <0.005). Myocardium of ICM is more severely damaged than that of NCM. Thus, noninvasive SPECT imaging with 123I-BMIPP is helpful in distinguishing patients with severe left ventricular dysfunction secondary to coronary artery disease from those with nonischemic cardiomyopathy.