High frequency jet ventilation (HFJV) via a triple-lumen endotracheal tube has been reported for the support of human infants. However, the triple-lumen tube may be undesirable in preterm infants because of the tube's comparatively small lumen for gas flow and for endotracheal suctioning and because of the risks of reintubation if a conventional tube has to be replaced for HFJV. We therefore studied the new Sechrist Model 990 high frequency jet ventilator, which uses a conventional single-lumen endotracheal tube, in normal and lung-injured adult rabbits. Methods: We first studied conventional mechanical ventilation (CMV) and HFJV at rates of 300, 600, and 900 breaths/min to determine the jet ventilator's effect on pulmonary gas exchange and hemodynamics in 18 normal rabbits, seeking to establish optimal HFJV settings. We then compared HFJV and CMV in 10 lung-injured rabbits. Lung injury was created by intravenous injection of oleic acid, which produced severe hemorrhagic pulmonary edema and alveolar-capillary block. Results: Compared to CMV, HFJV in the normal rabbits was associated with adequate gas exchange at lower mean airway pressures (P̅aw) at rates of 300, 600, and 900 breaths/min; and significantly higher mean arterial blood pressure at rates of 300 and 600 breaths/min. In the lung-injured rabbits, when compared to CMV, HFJV at 300 breaths/min produced improved ventilation and significantly higher arterial blood pressure, central venous pressure, and pH, while P̅aw was lower. Conclusions: These findings suggest a beneficial effect of HFJV and a method that can provide this ventilation with a standard single-lumen endotracheal tube rather than the triple-lumen tube often employed in HFJV, which may be undesirable in preterm human infants.