Antenatal corticosteroids in preterm pregnancy may result in the reduction of the incidence of respiratory distress syndrome (RDS) and neonatal mortality. It is well known that postnatal use of surfactant in very low birth weight (VLBW) infants with RDS results in decreased neonatal morbidity and mortality. To evaluate the additive beneficial effects of combined antenatal corticosteroids and postnatal use of rescue surfactant on the outcome of VLBW infants, we retrospectively reviewed 286 maternal/infant charts of preterm infants with gestational ages 23 to 32 weeks and birth weights 501 to 1500 gm who were born at our institution from 1991 through 1994. Of the 87 (30%) infants who were treated with corticosteroids before birth, 41 (47%) had RDS, and of the 199 (70%) infants who were not treated with corticosteroids before birth, 162 (81%) had RDS (p < 0.001). The infants who had RDS and who were treated with corticosteroids before birth had a decreased incidence of pulmonary air leaks and a decreased need for diuretic therapy. In addition, they had a significant reduction in O2 requirement and ventilator settings as reflected by FIO2, mean airway pressure, ventilator rate, O2 index, and A-aDO2 before they received the first dose of rescue surfactant (p < 0.05 to p < 0.01) in contrast to other VLBW infants who had RDS and who were not treated with corticosteroids before birth. We conclude that antenatal corticosteroid therapy in threatened premature labor combined with the use of postnatal rescue surfactant is associated with a decreased incidence of RDS and may be beneficial for reducing the severity of RDS and improving the eventual outcome of VLBW infants.