Macrosomia is characteristic of the infant whose mother has undiagnosed diabetes mellitus during pregnancy or whose diabetes has been inadequately controlled. Animal models of diabetes have included effects of pancreatectomy or beta-cell destruction by chemical agents. Maternal effects have been variable as have been effects on the fetus. Recent studies by Van Assche indicate that chemically induced diabetes may have genetically transmitted effects through three generations in rats. End-organ effects of hyperinsulinemia have been produced in normal fetal rhesus monkeys without maternal hyperglycemia. In this model, macrosomia and selective organomegaly similar to changes observed in the human infant of the diabetic mother were produced. Hepatic enzyme activities concerned with lipogenesis were increased, while some of those controlling gluconeogenesis were decreased. The primary effects of insulin in utero appear to accelerate growth.