Seventeen ventilator-dependent premature infants with bronchopulmonary dysplasia (BPD) were enrolled in a double-blind, placebo-controlled study to determine the effects of 3 days of intravenously administered dexamethasone (0.5 mg/kg/day) on pulmonary function, pulmonary inflammation, and the requirement for respiratory support (FIO2, ventilator peak pressure [PP], and respiratory rate [RR]). Assessment of pulmonary function included measurement of FVC, flow at 25% vital capacity (V25), and static compliance of the respiratory system (Crs), whereas pulmonary inflammation was assessed by the neutrophil count, ratio of elastase/2 x alpha-1-antitrypsin, and the concentrations of albumin and fibronectin in the tracheobronchial lavage (TBL) fluid. After 3 days of placebo treatment there were no significant changes in any of the measured parameters. In contrast, the dexamethasone-treated group demonstrated a significant decrease in respiratory support (FIO2: 50 versus 36%; PP: 21 versus 16 cm H2O; RR: 22 versus 14 breaths/min) and improved pulmonary function (Crs: 0.63 versus 0.85 ml/cm H2O/kg; V25: 23 versus 68 ml/s/kg). In addition, pulmonary inflammation was suppressed in the dexamethasone-treated group (neutrophils: 23 versus 11 x 10(4)/mg albumin: elastase/2 x alpha-1-antitrypsin: 0.24 versus 0.10; albumin: 7.1 versus 3.5 mg/dl; fibronectin: 33 versus 17 micrograms/mg albumin). We conclude that short-term treatment with dexamethasone improves pulmonary function and suppresses pulmonary inflammation as well as decreasing the respiratory support required by ventilator-dependent premature infants with BPD.