In a randomized multicenter trial, involving the collaboration of eight European neonatal intensive care units, the efficacy of replacement therapy with a new surfactant preparation (Curosurf) was tested in 146 patients with severe neonatal respiratory distress syndrome. Criteria for entry included birth weight 700 to 2,000 g, age when treated two to 15 hours, and requirement of artificial ventilation with FiO2 greater than or equal to 0.6. The babies were treated with a single large dose of surfactant (200 mg/kg) at a median age of nine hours (range two to 15 hours). Average FiO2 before treatment was the same (0.80) for both surfactant-treated patients and control patients. Babies receiving surfactant showed, within five minutes, a dramatic improvement of oxygenation as reflected by a nearly threefold increase of the PaO2/FiO2 ratio. Six hours after randomization, the PaO2/FiO2 ratio still showed a 98% improvement in surfactant-treated patients compared with controls (P less than .001), and statistically significant differences in favor of the treated babies persisted until 48 hours after randomization, when surviving control infants began to recover. Treatment with surfactant decreased neonatal (less than or equal to 28 days) mortality from 51% to 31% (P less than .05). Compared with control babies, the surfactant-treated group also had a decreased incidence of pulmonary interstitial emphysema (23% v 39%; P less than .05) and pneumothorax (18% v 35%; P less than .05). The percentage of survivors without bronchopulmonary dysplasia in the treated group was more than twice that of the control group (55% v 26%; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)