Non-insulin-dependent diabetes mellitus (NIDDM) occurs predominantly after the age of 50 years but is not easy to distinguish from late onset insulin-dependent diabetes. It is likely that misclassification is rare in a Caucasian population. Whilst NIDDM is widely believed to be genetically determined, recent epidemiological observations have consistently revealed statistical associations between indices of poor fetal and infant growth with susceptibility to loss of glucose tolerance in adult life. A possible explanation of these observations is that environmental constraints on fetal growth lead to permanent changes in organogenesis such that a poor capacity of insulin secretion and insulin resistance result. It is postulated that these adaptive responses serve to preserve the growth of certain organs, such as the brain, at the expense of others, such as the viscera. In addition, alterations in the function of organs, such as the liver, serve to aid survival of the offspring under conditions of poor postnatal nutrition. The results of studies of an animal model in which pregnant rats were fed a reduced protein diet are consistent with these concepts.