The aim of this study was to determine whether early administration (2 hours after the first surfactant dose) of the second surfactant dose would be superior to late surfactant treatment (6 hours after the first surfactant dose) in preterm infants with severe respiratory distress syndrome. Between June 2003 and March 2005, 40 newborns born with respiratory distress syndrome in Uludağ University Hospital were investigated in this prospective study. The inclusion criteria for the recruitment of the infants were: age < or = 2 hours, birth weight between 600-2500 g, gestational age between 24-36 weeks, X-ray consistent with respiratory distress syndrome, and need for mechanical ventilation with inspiratory oxygen fraction > or = 0.4 and mean airway pressure > or = 7 cm H2O to obtain arterial pressure of oxygen between 70-80 mmHg. Infants with lethal congenital anomalies or being treated with high-frequency oscillatory ventilation were excluded from the study. Birth weight, gestational age, gender, and Apgar scores were recorded and complications of the surfactant therapy were examined. Twenty boys and 20 girls were enrolled in the study. The first surfactant dose was administered in the first hour of life in all infants. The second surfactant dose was given 2 hours after the first dose in 20 of them and 6 hours after the first dose in the other 20. Infants in both groups (early versus late) were similar with respect to gestational age, birth weight, gender, and the rate of prenatal corticosteroids. There were also no significant differences between the two groups in terms of the response to surfactant therapy and complications. The results of this study show that administration of the second surfactant dose earlier is as effective as late administration, and it may be suggested that the second surfactant dose can be applied earlier in severe respiratory distress syndrome.