We studied a 29-year-old woman with myopathy since childhood with evidence of mitochondrial DNA (mtDNA) depletion. Muscle biopsy sample showed cytochrome c oxidase (COX)-negative fibers. Biochemistry showed COX deficiency. Southern blot analysis showed 76% depletion of mtDNA as compared with controls. This patient's clinical course suggests that long survival is possible in some patients with mtDNA depletion.