SummaryA 3‐week‐old girl with failure to thrive and cardiomegaly died of cardiac arrest at age 4 weeks. Morphologic studies of the heart showed enlarged muscle fibers with large accumulations of mitochondria, characteristic of histiocytoid cardiomyopathy. Biochemical studies showed markedly decreased succinate‐cyto‐chromecreductase and rotenone‐sensitive NADH‐cytochromecreductase activities, while other mitochondrial enzymes were normal. In isolated mitochondria, cytochrome spectra showed a severe defect of reducible cytochromeband a less marked defect of cytochromecc1, while the content of cytochromeaa3(cyto‐chromecoxidase) was normal. Histiocytoid cardiomyopathy appears to be due to a defect of complex III (reduced coenzyme Q‐cytochromecreductase) in the respiratory chain of heart mitochondria.