Treatment of nonhuman primate fetuses with epidermal growth factor (EGF) results in histologie and biochemical maturation of their lungs. To determine whether these effects improve lung function postnatally, we studied premature rhesus infants delivered at 78% of gestation afterin uterotreatment with EGF (n = 5) or placebo (n= 5). Indices of lung function during the 4 d of postnatal care included fractional concentration of inspired oxygen, peak inspiratory pressure, ventilator rate, mean airway pressure, arterial to alveolar oxygen tension ratio, and ventilation index. Statistically significant differences were noted in the time courses of these variables between EGF- and placebo-treated infants. The direction of the differences indicated that the EGF-treated infants had less severe lung disease. Surfactant apoprotein A concentration and lecithin to sphingomyelin ratio were both significantly higher in the amniotic fluid of the EGF-treated group, indicating advanced biochemical maturation in this group of animals. Whereas birth weight was not affected by EGF exposure, adrenal and gut weights, standardized for body weight, were increased significantly. Histologie studies showed advanced cellular maturation with increased parenchyma! airspace and decreased parenchyma! tissue space in the EGF-treated group compared with the control group. We conclude that prenatal exposure to EGF stimulates biochemical and histologie maturation of the lung and markedly attenuates the clinical severity of respiratory disease in this model of simian respiratory distress syndrome.