Cardiomyopathy is one of the main features that determines prognosis in patients with mitochondrial encephalomyopathy. We investigated respiratory chain failure using 99m Tc-MIBI- and 123 I-BMIPP-SPECT in vivo in five patients with mitochondrial cardiomyopathty. With the lowering of cardiac function, the 99m Tc-MIBI-washout rate (WOR) increased, and the 99m Tc-MIBI-uptake decreased, conversely. In patients who showed severe cardiac involvement, 99m Tc-MIBI-uptake was markedly reduced, and by contrast, 123 I-BMIPP-uptake increased ( 123 I-BMIPP/ 99m Tc-MIBI mismatch). There were significant correlations between the WOR on 99m Tc-MIBI-SPECT and interventricular septal thickness (IVST) on echocardiography and between WOR and left ventricular ejection fraction (LVEF) on 99m Tc-MIBI-SPECT. The increased WOR and decreased uptake of 99m Tc-MIBI were reflected by the lowered mitochondrial membrane potential created by mitochondrial respiratory chain whereas 123 I-BMIPP/ 99m Tc-MIBI mismatch may be created by the enhanced triglyceride-pool. These nuclear medicine techniques are the potential tools to evaluate the energy state in mitochondrial cardiomyopathy.