In the past few years the general medical profession has gradually become aware of the existence of a clinical syndrome characterized by the periodic occurrence of spontaneous hypoglycemia with its resulting symptoms relieved dramatically by the administration of sugar. The association of hypoglycemia with an overdose of insulin and the concept of endogenous hyperinsulinism, proposed by Harris 1 in 1924 and established by Wilder and his co-workers 2 in 1927 have led to the widespread misconception that hyperinsulinism is synonymous with spontaneous hypoglycemia. To be sure, hyperinsulinism is one of the most important causes of periodic spontaneous hypoglycemia in man. But, as will be indicated, there are many other abnormalities which produce an abnormally low level of the blood sugar and which, consequently, produce the same train of symptoms. Thus, in any case in which it is suspected that symptoms are due to hypoglycemia, the presence of abnormally low levels of blood sugar must be demonstrated during attacks and the symptoms in question relieved promptly by the administration of sugar. This establishes only the nonspecific diagnosis of spontaneous hypoglycemia. The etiologic diagnosis must now be sought by every diagnostic method at our disposal, for on the etiologic diagnosis rests the indicated therapeutic procedure. It is evident, for example, that an explora¬ tory operation, designed to discover a pancreatic insuloma, will be a useless and dangerous procedure when the hypoglycemia results from hypofunction of the pituitary or adrenal glands or when it is due to a disturbed glycogenic mechanism of the liver.It is beyond the scope of this presentation to discuss individually each of the possible causes of spontaneous hypoglycemia. It is evident that many of these etiologic factors will appear infrequently in patients with proved spontaneous hypoglycemia. It can be calculated from YVilder's 23 figures of etiologic incidence that, of fiftyfive patients with manifestations of hypoglycemia in whom fasting blood sugar levels of 60 mg. per hundred cubic centimeters or below were obtained, forty-one cases (75 per cent) were classified as falling into one of three groups, namely hyperinsulinism (organic type), neurosis (functional hyperinsulinism in our classifica¬ tion) and hepatic disease. Similarly, in an analysis of 278 cases of so-called spontaneous hypoglycemia reported by Martin and Hellmuth -4 only thirteen cases are found in which there were definite symptoms of hypoglycemia and in which fasting blood sugar levels below 60 mg. per hundred cubic centimeters were obtained. Ten of the thirteen cases (76 per cent) were listed as being due to organic hyperinsulinism, func-ETIOLOGIC CLASSIFICATION OF SPONTANEOUS HYPOGLYCEMIA I. Organic-recognizable anatomic lesion, (o) Hyperinsulinism.