To explain som e of the effects of prenatal glucocorticoid treatment on lung function, surfactant paramet ers in the airway specimens of ventil ator-dependent preterm infants were analyzed . In this double -blind study, the mother s of these infants had received dexam ethasone (DEX) or placebo prenatally. Human surfactant was give n for the treatment of moderate to severe respiratory distress syndrom e. Seventy-six preterm infants with mean gestational age of 29 wk and mean birth weight of 1137 g wer e studied. The concentrations of surfactant comp onents in epithelial lining fluid (ELF) were analyz ed, and the surfac e activity was measured using a pulsating bubble meth od. Prenat al DEX treatment increased the responsiveness to exogenous surfactant and decreased the seve rity of respiratory failure durin g the first day of life. The treatment had no effect on the concentrations of surfactant phospholipid s that were generally high. Prenat al DEX treatment incr eased the association between phospholipid conc entration in ELF and the degre e of respir atory failure . Prenatal DEX improved the surface activity of surfactant isolated from airway speci mens and tended to increase the ratio of surfactant protein A to phosph atidylcholin e among recipients of exogenous surfactant. A subgro up of infants , offspring of Several randomized studies have shown that prenatal glucocorticoid treatment before preterm delivery improves survival and decreases the incidence of RDS in preterm infants (1). Likewise, treatment with both natural and synthetic surfactants decreases the mortality of very low birth weight infants and the severity of RDS (2). In newborn infants with RDS, exogenous surfactant therapy improves gas exchange, functiona l recidual capacity, and dynamic compliance (3). A retrospective analysis of surfact ant trials suggests that the combination therapy of prenatal glucocorticoid and exogenous Received December 27, 1994; accepted May 9, 1995 676 moth ers with severe hypert ension had an abnormally low concentration of surfactant protein A and a poor outcome, despite prenat al DEX treatm ent or surfactant sub stitution. Prenatal DEX decreased the concentration of nonsedim entable proteins in ELF and decreased the inhibition of surface activity by these protein s. Our results indicate that imp roved surfactant function during the first day of life explains some of the beneficial pulm onary effects of prenatal glucocorticoid treatment in preterm infants who are ven tilator-depe ndent. (Pediatr Res 38: 676-684, 1995)