['To characterize the clinical features of infants who do not respond to surfactant therapy.', 'Patient series, chart review.', 'Academic referral neonatal intensive care unit. PATIENTS/SELECTION: Ninety-nine consecutive infants with respiratory distress syndrome who received surfactant therapy and 107 infants from the 2 years prior to initiation of surfactant therapy matched for birth weight, race, sex, gestational age, chronological age, and disease severity.', 'Oxygen index was used to quantitate response to surfactant therapy. A 25% decrease in oxygen index 6 hours after the first surfactant dose was significantly different from that of the matched historical cohort (P = .04). Oxygen index decreased 25% or more in 49 infants, the response group, while oxygen index decreased less than 25% or increased following therapy in the remaining 50 infants, the nonresponse group. Pulmonary interstitial emphysema occurred more frequently in the nonresponse group. The only deaths from pulmonary causes at 10 days of age or younger occurred in the nonresponse group (n = 11).'] Does surfactant therapy failure identify infants at risk for pulmonary mortality?