We evaluated the routine use of dexamethasone for the prevention of postextubation respiratory distress by entering 60 ventilated infants into a prospective, randomized, blinded study. Thirty minutes before extubation, 30 infants were given a single dose of intravenous dexamethasone (0.25 mg/kg), and 30 infants received saline placebo. Infants were intubated orotracheally for at least 48 hours following a single intubation and were maintained on low ventilator settings (F10(2) less than 0.35, intermittent mandatory ventilation [IMV] less than 6, positive end-expiratory pressure [PEEP] less than 4) at least 12 hours before extubation. Following extubation, all infants weighing less than 1500 g were routinely placed on nasal continuous positive airway pressure (NCPAP). There was no difference between the two groups in postextubation Downes' score, serum pH, PCO2, or oxygen requirement at 30 minutes, 6 hours, and 24 hours. Respiratory acidosis occurred in one steroid-treated patient and in two placebo-treated infants. Stridor occurred in four infants in each group. No infant developed postextubation lobar atelectasis or required reintubation. We conclude that prophylactic administration of dexamethasone does not improve the immediate postextubation course of infants following a single intubation and that its routine use at the time of extubation is not indicated.