We compared the tracheobronchial histopathology seen after conventional mechanical ventilation (CMV) and high-frequence jet ventilation (HFJV) in 44 adult cats. Two different HFJV humidity systems were examined: one used entrained mist alone, and the other infused 3 ml/kg·h of 0.45% NaCl directly into the jet stream. HFJV produced more tracheal damage than CMV. This damage occurred at the endotracheal tube tip. The pattern of injury was acute inflammation, with erosion, necrosis, and infiltration of polymorphonuclear (PMN) leukocytes. The HFJV humidity system using entrained mist alone produced more damage than the HFJV infusion-pump humidity system. HFJV also produced more luminal mucus at all airway levels. Lower airways had different injury patterns. After 16 h, CMV produced more histopathology in the carina and mainstem bronchi. Here, the injuries were losses of surface cilia, losses of epithelial goblet cells, and inflammation. The dissimilar histologic injury patterns seen with 2 different forms of mechanical ventilation suggest different mechanisms of injury.