METHODS We compared tracheal histologic injury patterns, airway pressure (Paw) requirements, and in vivo and in vitro estimate of airway humidification in 13 adult cats with normal lungs mechanically ventilated for 16 hr. Six animals were treated with high-frequency jet ventilation at 400 breaths/min and seven animals with high-frequency oscillatory ventilation at 900 breaths/min. RESULTS Peak airway pressure, Paw, mean Paw, and end-expiratory pressure requirements were significantly higher for high-frequency oscillatory ventilation as compared with high-frequency jet ventilation for similar gas exchange (p less than .01). While in vivo estimates of airway humidification suggested progressively greater H2O delivery into the respirator circuit, and therefore the airway, with higher frequencies, the in vitro study suggested similar relative humidities of the delivered gases during both types of mechanical ventilation. Tracheal injury, measured using a semiquantitative scoring system, was scored similarly for both ventilators studied despite the higher pressure requirements seen with the high-frequency oscillator. CONCLUSIONS In this animal model, high-frequency ventilation using either jet or oscillation techniques produced similar inflammatory tracheal damage despite differences in Paw exposure and humidity.