Eight children suffering from periodic episodes of clinical hypoglycemia were studied. A constant association of ketosis preceding symptoms and of low blood sugar values was noted. Long intervals of normal blood sugar values and of good health intervened between the short periods of metabolic derangement. The clinical disease could be reproduced by the feeding of a low-calorie ketogenic diet. Although a depletion of hepatic glycogen was a constant finding at the height of symptoms, it appeared that the pathologic mechanism was related to a failure of adaptation to a fat-burning economy.