Surfactant rescue therapy can be utilized effectively early in the course of respiratory distress syndrome (RDS) in infants weighing > 1,000 g and treated exclusively with continuous positive airway pressure (CPAP) therapy. Thirteen infants (BW, 1,774 +/- 580 g; GA, 31 +/- 3 weeks) comprising the CPAP/SURFACTANT group were compared with 12 infants (BW, 1,753 +/- 556 g; GA, 31 +/- 2 weeks) who comprised the intermittent mandatory ventilation (IMV)/surfactant group, and with 14 infants (BW, 1,776 +/- 332 g; GA, 32 +/- 2 weeks) treated with CPAP before surfactant was clinically available. A 5 mL/kg dose of Exosurf Neonatal (Burroughs-Wellcome) was administered to infants intratracheally when the FiO2 requirement reached 0.40 to maintain the PO2 above 50 torr. Infants in the CPAP/surfactant group were intubated solely for surfactant administration and extubated within 18 +/- 6 min of treatment. The CPAP/surfactant group was treated at a mean age of 12.3 +/- 9.3 h, and the IMV/surfactant group at 10.2 +/- 9.8 h. Alveolar-arterial oxygen gradient (AaDO2), oxygenation index (OI), and mean airway pressure (MAP) were determined immediately before and after surfactant therapy, and at comparable times for the CPAP-only group. A significant difference was found in pre-treatment AaDO2, OI and MAP between the CPAP/surfactant group and IMV/surfactant group, but not between the CPAP/surfactant group and the CPAP-only group. Similarly, a significant difference in AaDO2, OI and MAP continued post-treatment was noted. However, a significant difference was also found at this time between the CPAP/surfactant group and the CPAP-only group. In addition, a significant difference was noted in AaDO2 and OI pre- and post-treatment within each surfactant-treated group. Furthermore, in the CPAP-only group AaDO2 and OI actually worsened (212 +/- 70 vs. 239 +/- 68; 4.0 +/- 1 vs. 4.5 +/- 2, respectively). There was a significant reduction in the duration of oxygen therapy (3 +/- 2 vs. 5 +/- 2 vs. 4.5 +/- 2 days, respectively) as well as in the total days of hospitalization (30 +/- 10 vs. 42 +/- 15 vs. 43 +/- 12 days, respectively). We conclude that in this small group of infants surfactant administration was effective and safe. It appeared to improve the course of RDS and shorten the duration of oxygen exposure and days of hospitalization.