The lungs of anesthetized rabbits were embolized by intravenous injection of 75 mg/kg of starch particles in divided doses. One group received high-frequency oscillatory ventilation (HFOV) at a rate of 15 Hz. Both groups were ventilated with an FIO2 of 1.0. After 3 hr of ventilation, the animals were sacrificed, and the extravascular lung water (EVLW) was determined gravimetrically. With conventional mechanical ventilation (CMV), the EVLW/body weight ratio was 4.1 +/- 1.4 g/kg (mean +/- SD) and was significantly higher than the ratio of 2.8 +/- 0.6 in animals given HFOV (P less than 0.05). In a second series of animals, 20 muCi of 125I-labeled bovine albumin was injected intravenously prior to embolization and followed by the same two types of ventilation. After the rabbits were sacrificed, the lungs were lavaged with 0.9 N saline, and the radioactivity of the fluid was measured to determine the protein leak. After CMV, 2.76 +/- 2.05% of the injected radioactivity was recovered from the fluid, significantly higher (P less than 0.01) than the amount of radioactivity recovered after HFOV, 0.3 +/- 0.28%. There also was significantly more labeled protein in the lung tissue that had been on CMV. We conclude that in this model of pulmonary edema, HFOV significantly reduces both the amount of fluid and protein leaking into the lung.