OBJECTIVE The goal was to establish whether reduced amounts of pulmonary surfactant contribute to postextubation respiratory failure in preterm infants recovering from respiratory distress syndrome. METHODS We prospectively recruited preterm infants who needed mechanical ventilation and exogenous surfactant for treatment of moderate/severe respiratory distress syndrome and could not be extubated before day 3 of life. (13)C-labeled dipalmitoyl-phosphatidylcholine was administered endotracheally as tracer before extubation, for estimation of surfactant disaturated phosphatidylcholine pool size and half-life. Patients were retrospectively divided into 3 groups, that is, extubation failure if, after extubation, they needed reintubation or continuous positive airway pressure treatment of >or=6 cmH(2)O and fraction of inspired oxygen of >0.4, extubation success if they did not meet the failure criteria, and not extubated if they needed ongoing ventilation. Clinical and respiratory parameters were recorded hourly. RESULTS Reliable kinetic data could be obtained for 63 of the 88 enrolled neonates. Sixteen, 23, and 24 neonates were categorized in the extubation failure, extubation success, and not extubated groups, respectively. Clinical and demographic characteristics did not differ between the extubation failure and extubation success groups. Disaturated phosphatidylcholine pool size was smaller in the extubation failure group than in the extubation success group (25 +/- 12 vs 43 +/- 24 mg/kg) and was 37 +/- 32 mg/kg in the not extubated group. Disaturated phosphatidylcholine half-life was 19 +/- 7, 24 +/- 12, and 28 +/- 18 hours in the extubation failure, extubation success, and not extubated groups, respectively. CONCLUSIONS In a selected population of preterm infants with moderate/severe respiratory distress syndrome who could not be extubated in the first 3 days of life, infants who were reintubated or needed high continuous positive airway pressure settings after extubation had a smaller disaturated phosphatidylcholine pool size than did those who were successfully extubated or needed low continuous positive airway pressure settings.