When normal lungs are ventilated with large tidal volumes (VT) and end-inspired pressures (Pei), surfactant is depleted and pulmonary edema develops. Both effects are diminished by positive end-expiratory pressure (PEEP). We reasoned that ventilatory with large VT-low PEEP would similarly increase edema following acute lung injury. To test this hypothesis, we ventilated dogs 1 h after hydrochloric acid (HCl) induced pulmonary edema with a large VT (30 ml/kg) and low PEEP (3 cm H2O) (large VT-low PEEP) and compared their results with dogs ventilated with a smaller VT (15 ml/kg) and 12 cm H2O PEEP (small VT-high PEEP). The small VT was the smallest that maintained eucapnia in our preparation; the large VT was chosen to match Pei and end-inspired lung volume. Pulmonary capillary wedge transmural pressure (Ppwtm) was kept at 8 mm Hg in both groups. Five hours after injury, the median lung wet weight to body weight ratio (WW/BW) was 25 g/kg higher in the large VT-low PEEP group than in the small VT-high PEEP group (p less than 0.05). Venous admixture (Qva/Qt) was similarly greater in the large VT-low PEEP group (49.8 versus 23.5%) (p less than 0.05). We conclude that small VT-high PEEP is a better mode of ventilating acute lung injury than large VT-low PEEP because edema accumulation is less and venous admixture is less. These advantages did not result from differences in Pei, end-inspiratory lung volume, or preload (Ppwtm).(ABSTRACT TRUNCATED AT 250 WORDS)