A randomized controlled trial of Exosurf Neonatal, a synthetic exogenous surfactant, was performed. Exosurf was given to premature infants weighing 700-1350 g, by instillation down the endotracheal tube during mechanical ventilation, within 1 h of birth. Control infants were treated with air. Dose administration was performed in secrecy by clinicians who maintained the blind for 2 years. A total of 109 infants received air and 109 received Exosurf; 19 infants with congenital pneumonia or major malformations were excluded from the primary efficacy analysis. By the age of 28 days there were 14 deaths in the air group and 4 deaths in the Exosurf group, a 69% reduction with Exosurf (P = 0.020). Survival without bronchopulmonary dysplasia at the age of 28 days was significantly improved by 15% (P = 0.050). By the age of 1 year post-term there were 19 deaths in the air group and 10 deaths in the Exosurf group, a 42% reduction with Exosurf (P = 0.104). There were no significant changes in the incidence of bronchopulmonary dysplasia, pulmonary air leaks, intraventricular haemorrhage, patent ductus arteriosus, necrotizing enterocolitis or infection. The reduction in mortality indicates important results in high risk premature infants treated soon after birth with a single dose of Exosurf.