High-frequency jet ventilation (HFJV) was compared with conventional ventilation ventilation during oleic acid-induced pulmonary edema in dogs. HFJV, when combined with positive end-expiratory pressure (PEEP), returned arterial PO2 (PAO2) and venous admixture to preoleic acid levels, even with tidal volumes as low as 4.8 ml/kg and rates of 300 min-1. When HFJV was compared with conventional (low-frequency, high tidal volume) ventilation at the same Flo2 and level of PEEP, Pao2 was lower and venous admixture higher with HFJV. However, venous admixture was lower with HFJV when comparisons were made at the same peak airway pressure, because of a higher level of PEEP compared with conventional ventilation. At each level of PEEP, cardiac and stroke indices were not different between the two methods of ventilation. The ability to eliminate CO2 with lower peak airway pressures or to increase PEEP without further increases in peak airway pressure are the primary advantages of HFJV during severe lung injury. Oxygenation is as efficient during HFJV as during conventional ventilation in this model of pulmonary edema when comparisons are made at the same peak airway pressure, but less efficient at the same PEEP.