Spontaneous hyperglycemia, hyperinsulinemia and obesity are common features for at least one period of the lifetime in some strains of mice. Both genetic and environmental factors are involved in the pathogenesis of the diabetes-like syndrome, making these strains excellent models for studies in both obesity and diabetes-like states. The metabolic peculiarities can be due to a dominant gene, as for the yellow obese, or a single recessive gene, as in the obese and the diabetes mouse; or they can be of polygenic origin, as for the KK and the NZO mouse. However, the severity of the metabolic disorder is due to the interaction of the mutant genes iwth modifiers in the bat genes themselves. Studies on the pathophysiology and biochemistry of these animals have revealed interstrain differences, different patterns of development of the metabolic disorder, and different degrees of severity of the diabetes-like syndrome. Although the primary causes of the syndrome remain unclear in some strains, an involvement of hypothalamic feeding centers has been implicated.