The spontaneous diabetes of the BB Wistar rat has many homologies to that of human insulin-dependent diabetes mellitus (IDDM). The different degrees of severity and varying time courses of the islet lesion lead to a spectrum of metabolic derangements and corresponding clinical presentations. Thus, animals with the diabetic phenotype may show only mild insulitis, more severe insulitis with glucose intolerance, marked beta cell destruction with overt but stable diabetes, or total beta cell loss with classic IDDM. Progression of the lesion and clinical presentation occur, as well as occasional reversion to less severe forms. Hence, the definition of a susceptible animal as nondiabetic requires demonstration of normal islets and normal glucose tolerance. In animals showing sustained impaired glucose tolerance (IGT), insulin secretion is most commonly impaired in response to glucose and tolbutamide, though not necessarily to arginine. However, a subgroup with IGT shows hyperinsulinemic responses. Glucagon secretion appears normal in IGT. With overt IDDM, insulin levels are low and unresponsive. However, inappropriate normoglucagonemia, and abnormal regulation of IRG secretion by arginine and neural factors accompany IDDM. This "model" syndrome has already demonstrated its utility for insights into the pathophysiology of IDDM, many of which may be applicable to the further study of the analogous human syndrome.