Childhood obesity most often develops in the absence of a gross disturbance in hormonal function. Hypothyroidism, Cushing's syndrome, and growth hormone deficiency are specific hormonal disorders that can result in a relative increase in adipose tissue; these conditions are, however, rare etiologies of childhood obesity. Insulin resistance commonly accompanies obesity in both children and adults, and the role of hyperinsulinemia as a cause of excess adipose tissue has been well documented in the human fetus and newborn. Insulin, in addition to its role in the regulation of carbohydrate metabolism, appears to be an important fetal growth factor.'S2 Hyperinsulinemic fetuses, such as infants of diabetic mothers and infants with Beckwith-Wiedemann syndrome tend to be large at birth. By contrast, insulinopenic neonates with pancreatic agenesis or syndromes characterized by severe insulin resistance are small with decreased subcutaneous fat. Though these perinatal effects of insulin upon growth are well documented, the possible long-term effects of in utero exposure to high insulin concentrations have not been explored. The neonatal effects of maternal diabetes mellitus are best understood within the framework of the modified Pedersen hypothesis (FIG. 1). Herein, it is suggested that whenever maternal insulin is inadequate, multiple maternal fuels are disturbed and that these fuels gain increased access to the fetus where they stimulate growth and effect premature activation of fetal insulin secretion. Fetal growth should be critically skewed by the increased insulin activity so that insulin responsive sites, a This study was funded in part by National Institutes of Health Grants HD 11021, HD 19070, HD 62903, HD 23141, DK 10699, and RR 48; Training Grant DK 07169; and a Grant from the Ronald McDonald Foundation.