Recurrent rhabdomyolysis due to decreased glycolysis occurred during strenuous exercise by patients with lactate dehydrogenase-A subunit (LDH-A; muscle) deficiency. We report the glycolytic features of 4 patients from 2 families in whom the severity of the disease differed. There was no difference in the gene abnormality. The enzyme activity of LDH in the muscle was less than 5% that of the control value. Glycolysis in the muscle showed that the respective sums of the pyruvate and lactate levels in the patients with mild and severe symptoms were reduced to approximately 65% and 35% that of the control value. Comparable amounts of glycerol 3-phosphate were produced. Glycerol 3-phosphate dehydrogenase activity in the muscles of patients with mild symptoms was three times the control value. These findings suggest that the disease severity in our patients may be related to the degree of NADH reoxidation by glycerol 3-phosphate dehydrogenase substituting for LDH.