The effect of natural surfactant on respiratory system mechanics in infants with respiratory distress syndrome (RDS) is incompletely understood, possibly because the analysis has usually been confined to the tidal breath. We studied 11 paralyzed neonates weighing 540 to 1,850 g before and approximately 30 min after surfactant, which was instilled at 4 to 41 h of age. Diagrams relating airway pressure to expired volume were obtained by having the infant exhale passively through a flowmeter, starting at 30 and ending at 0 cm H20 of pressure. An interrupter intermittently stopped the flow so that pressure could be recorded under static conditions. FRC was measured by sulfur hexafluoride washout, and TLC was calculated from FRC and the pressure-volume (P-V) curve. Ventilation homogeneity was assessed from the washout curve as pulmonary clearance delay (PCD). TLC increased by 10% or more in five infants, but it remained unchanged in the others. Median TLC was 19 ml/kg before and 21.5 ml/kg after surfactant (p = 0.39). The P-V curve became markedly steeper at low pressures after surfactant in most infants, the slope of the steepest segment, i.e., maximal compliance, increasing from 0.65 to 1.22 ml/cm H20/kg (medians, p = 0.008). Dynamic compliance (Cdyn) was unchanged at 0.28 ml/cm H20/kg, whereas specific dynamic compliance (Cdyn/FRC) decreased (p = 0.04). There was no significant immediate change in PCD. The findings imply that during the first 30 min surfactant acted mainly by stabilizing already ventilated air spaces.