26 preterm infants with severe respiratory distress syndrome (RDS) have been treated at different ages with a single dose of natural porcine surfactant (Curosurf, 200 mg/kg). Criteria for treatment included clinical and radiological signs of severe RDS (grade III-IV), requirement of artificial ventilation and an FiO2 greater than or equal to 0.6. Nineteen neonates have been subjected to early treatment (2-15 h of age, mean birth weight SD: 1201 +/- 387 g) and 7 patients to late treatment (greater than 15 h to 48 h of age, birth weight SD 1624 +/- 649 g). Average FiO2 before treatment was 0.88 in early-treated patients and 0.8 in late-treated patients, age at treatment was 4.6 h and 36 h, respectively (median). Both early- and late-treated infants exhibited an improvement in oxygenation (more than twofold increase of the PaO2/FiO2 ratio) within 5 minutes after initiation of therapy. Average duration of intermittent pressure ventilation was 15 days in the early treatment group and 19 days in the late treatment group. Total exposition to greater than 21% oxygen was 21 days in early-treated and 48 days in late-treated infants. Pneumothorax occurred in none of the patients. All early treated infants survived without signs of severe bronchopulmonary dysplasia (BPD greater than 21% O2, greater than 90 days plus radiological changes). However, two out of seven late-treated infants developed severe BPD; one patient died as a consequence of cardiopulmonary deterioration. Two patients in the early treatment group died of nonpulmonary complications. We conclude that surfactant replacement therapy should probably be initiated as soon as possible after manifestation of severe RDS.