Inflammatory chemical mediators, platelet-activating factor (PAF), thromboxane (TX) B2, and 6-keto-prostaglandin (PG)F1 alpha, were extracted from lung lavage fluid after conventional mechanical ventilation (CMV) and high frequency oscillatory ventilation (HFOV) to clarify the relation between mode of ventilation and lung injury in surfactant-depleted rabbit lungs. Anesthetized adult rabbits were tracheostomized, and surfactant depletion was induced by repeated saline lavage. Lung lavage for measurement of mediators was performed after 4 h of CMV at an FIO2 of 1.0 and a mean airway pressure of 15 cm H2O or HFOV (15 Hz) at an FIO2 of 1.0 or 0.21 and a mean airway pressure of 15 cm H2O. The number of total cells and polymorphonuclear leukocytes (PMN) and the levels of PAF, TXB2, and 6-keto-PGF1 alpha were measured by radioimmunoassay. Total respiratory compliance (Crs) was measured by the passive flow-volume curve method. The numbers of PMN, and the levels of PAF and TXB2 in lung lavage fluid were significantly greater during CMV than during HFOV. HFOV resulted in decreased production of PAF and TXB2 in a surfactant-depleted rabbit lung. Crs was significantly less during CMV than during HFOV. These results suggest that HFOV could prevent the release of such inflammatory chemical mediators and result in less lung injury than CMV.