The serum pyruvate and lactate levels were studied after exercise on a bicycle ergometer in a family of diabetes mellitus (DM) associated with a mutation at nucleotide 3243 in the mitochondrial gene. A 56-year-old Japanese woman with the mutation at a percentage of 5% in the blood had insulin-dependent DM and sensory hearing loss without muscle symptoms. Her serum lactate and pyruvate levels increased markedly during and after exercise on a bicycle ergometer. Two of her sons were found to have the same mutation at a percentage of 17% and 18%, respectively. Her 26-year-old son was found to have borderline DM after oral glucose loading, although he showed no abnormalities of the metabolism of pyruvate and lactate. Her 31-year-old son showed no abnormalities after oral glucose loading and after exercise on a bicycle ergometer. Although the same mutation causes more severe MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), little is known about whether these diabetic patients are subclinically involved with myopathy. The noninvasive ergometer exercise with determination of serum pyruvate and lactate may be useful in evaluating the severity of myopathy in these patients.