We measured oxygen consumption in the exercising lower limb by using noninvasive tissue oximetry with the near-infrared spectra of hemoglobin in the quadriceps muscle during bicycle ergometer exercise in four normal controls and three patients with chronic progressive external ophthalmoplegia (CPEO) as well as one patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Normal controls showed constant oxygenation during exercise and a rapid recovery after exercise. However, all four patients with mitochondrial myopathy showed abnormal oxygenation during exercise and a slow recovery afterward. The results reflected the defect in oxidative phosphorylation and the impairment in oxygen utilization in those patients. The distinctive patterns of imbalance between oxygen delivery and utilization correlated well with the severity of mitochondrial myopathy as judged by the sum of the serum lactate and pyruvate content during exercise. Noninvasive tissue oximetry may be useful to measure the severity of myopathy and exercise intolerance in patients with mitochondrial myopathy.