To understand the mechanisms behind the improved oxygenation after intratracheal surfactant instillation, the immediate effects of lung volume and pulmonary mechanics were analyzed. All infants studied were enrolled in multicenter trials in which surfactant therapy was instituted according to a rescue protocol. Infants received either synthetic surfactant (Exosurf) or modified porcine surfactant (Curosurf). Measurements of lung volume and pulmonary mechanics were successfully performed in 12 patients with a birth weight of 1.3 +/- (SD) 1.4 weeks. Functional residual capacity (FRC) and pulmonary mechanics were measured during mechanical ventilation. The FRC increased significantly by 70% (median), from 7.10 +/- (SD) 2.8 ml/kg to 11.5 +/- 3.3 ml/kg after surfactant instillation. However, a concomitant decrease in specific compliance was also seen. These findings could suggest that this immediate increase in FRC is initially nonuniform. However, since no significant correlation between changes in FRC and improvement in arterial-to-alveolar oxygen tension ratio is seen, other effects of surfactant must also be considered. These could include local and/or systemic changes in hemodynamics, such as decreased shunting as well as various effects on gas diffusion.