A description is given of two unrelated North American Indian children who, at 11 and 9 months of age respectively, were found to have metabolic acidosis, associated with a high concentration of lactate and pyruvate in the blood. Both children were mentally retarded, suffered from convulsions, and showed obesity and muscular hypotonia. Liver glycogen disease, diabetes mellitus, and chronic hypoxia were excluded in both cases. Decreased removal of pyruvate and lactate from the blood due to some, as yet, undetermined metabolic block appeared to be the most likely causative mechanism. As well as a defect in the metabolism of lactate and pyruvate, evidence of an abnormality of α-keto glutarate metabolism was found in one case.