Premature rabbit neonates delivered at gestational age 27 days were ventilated by high frequency oscillation for 60 min with 100% O2, using a frequency of 7-8 Hz, 50% inspiration time and mean airway pressures of 6-8 cm H2O. Twenty-five animals received bovine surfactant (2 ml/kg body weight; phospholipid concentration 85-100 mg/ml) in the tracheal cannula before onset of ventilation, and 22 littermates served as controls. In the surfactant-treated group, average tidal volume was about 10 times larger than in controls, yet only 15% of the estimated dead space. Judged from ECG recordings, the treated animals also had a much higher survival rate: 96 versus 5% (p<0.001). Morphometrically, mean alveolar volume density was increased in the surfactant-treated animals in comparison with controls: 0.65 ± 0.08 versus 0.37 ± 0.08 (x ± SD;p<0.005). Bronchiolar epithelial lesions were found in all control animals and were severe in almost all cases. In the surfactant-treated group, epithelial lesions were absent in 12, mild in 11, and fairly prominent in two animals. We conclude that after treatment with surfactant, the premature newborn rabbit can be ventilated adequately with high frequency oscillation at comparatively low mean airway pressures and that surfactant replacement effectively reduces the development of epithelial lesions in conducting airways during high frequency oscillation.