Different clinical features exist for lactate dehydrogenase A-subunit and B-subunit deficiencies. The metabolic basis for these clinical differences was elucidated by investigating carbohydrate metabolism in the affected tissues. Glycolysis was markedly retarded at the position of glyceraldehyde 3-phosphate dehydrogenase, and significant increases of glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, and fructose 1,6-diphosphate were observed. The physical and kinetic properties of glyceraldehyde 3-phosphate dehydrogenase prepared from human erythrocytes and skeletal muscle were almost identical, but the mode of inhibition of the enzyme was slightly different in erythrocytes and in skeletal muscle. In erythrocytes, impaired reoxidation of NADH followed by the deficiency of substrate NAD+ causes a reduction of glyceraldehyde 3-phosphate dehydrogenase activity. However, in skeletal muscle, the increased level of NADH markedly inhibits the enzyme under anaerobic conditions. A flux of triose phosphates from glycolysis occurred in skeletal muscle of a patient with A-subunit deficiency. This flux is attributable to the high cytosol alpha-glycerophosphate dehydrogenase activity in skeletal muscle. for these reasons the ATP production was significantly impaired in the patient and the damage to muscle cells brings about the release of cytosolic enzymes and muscle rigidity after hard exercise. In contrast in the erythrocytes, the level of alpha-glycerophosphate dehydrogenase is very low and another red cell-specific NADH reoxidizing system such as NADH-cytochrome b5 reductase (NADH-methemoglobin reductase) is operating. In this manner, the NAD+ level in erythrocytes is compensated for without the flux of triose phosphates derived from glucose. Therefore, the ATP production in erythrocytes is sufficiently maintained by glycolysis even in a patient with complete lactate dehydrogenase B-subunit deficiency. Thus, impaired ATP production in anaerobic stage is a condition which is specific for lactate dehydrogenase A-subunit deficiency but does not occur for B-subunit deficiency. The different clinical features of the A- and B-subunit deficiencies have been clearly elucidated.