BACKGROUND The immediate and regional effects of exogenous surfactant in open lung high-frequency oscillatory ventilated (HFOV) preterm infants are unknown. OBJECTIVE To assess regional changes in lung volume, mechanics, and ventilation during and after surfactant administration in HFOV preterm infants with respiratory distress syndrome (RDS). METHODS Using electrical impedance tomography, changes in lung volume were continuously recorded during a stepwise recruitment procedure before, during, and after surfactant administration in 15 preterm infants (gestational age: 28.3 wk; birth weight: 1,000 g). Deflation limbs of the pressure-impedance curve before and after surfactant were mapped and the effect of surfactant on oscillation volumes and ventilation was determined. Data were analyzed for the whole cross-section and the left, right, ventral, and dorsal lung regions. RESULTS Surfactant increased lung volume by 61 ± 39% within a median time of 241 seconds. The ventral to dorsal ratio in lung volume changed significantly from 1.16 before to 0.81 after surfactant administration. The upper inflection point of the deflation limb after surfactant (10.4 ± 2.4 cm H(2)O) was significantly lower compared with before surfactant (16.4 ± 3.1 cm H(2)O). Surfactant increased maximal compliance of the respiratory system, and this effect was reached at lower airway pressures. Surfactant caused a transient decrease in oscillatory volume but did not alter its regional distribution. CONCLUSIONS Surfactant treatment in HFOV preterm infants with RDS causes a rapid increase and subsequent stabilization of lung volume, which is most prominent in dependent lung regions. It increased maximal compliance, but this effect is only reached at lower airway pressures.