Because respiratory distress syndrome may result, in part, from a hormonal deficiency in the developing fetus, we investigated the endocrine millieu of 28 infants of women with diabetes who were delivered prematurely (34 to 37 weeks of gestation). The umbilical serum concentrations of estrone, estradiol, estriol, cortisol, and prolactin in infants of women with diabetes who developed respiratory distress syndrome (n = 6) were lower than those in infants of women with diabetes who had normal lung function. Serum hormone levels in age-matched newborns of normal women were higher than those in the infants of women with diabetes with respiratory distress syndrome but were not different than those in the infants of women with diabetes with normal lung function. Plasma glucose levels were highest in women whose neonates developed respiratory distress syndrome. An inverse correlation existed between maternal glucose levels and lecithin-sphingomyelin ratios in amniotic fluid. Thus diabetes occasionally results in significantly delayed maturation of the fetal endocrine milieu. In these instances, delayed fetal lung maturation is a frequent occurrence. Moreover, both phenomena may be related to the extent of diabetic control during pregnancy.