When normal lungs are ventilated with large tidal volumes (VT) and end-Inspired pressures (Pel), surfactant Is depleted and pulmonary edema develops. Both effects are diminished by positive end-expiratory pressure (PEEP). We reasoned that ventilation with large VT-Iow PEEP would similarly Increase edema following acute lung Injury. To test this hypothesis, we ventilated dogs 1 h after hydrochloric acid (Hel) Induced pulmonary edema with a large VT (30 ml/kg) and low PEEP (3 ern H20)(large VT-Iow PEEP) and compared their results with dogs ventilated with a smaller VT (15 mllkg) and 12 cm H20 PEEP (small VT-high PEEP). The small VT was the smallest that maintained eucapnla In our preparation; the large VT was chosen to match Pel and end-Inspired lung volume. Pulmonary capillary wedge transmural pressure (Ppwtm) wss kept at 8 mm Hg In both groupa. Five hours after Injury, the median lung wet weight to body weight ratio (WW/BW) wss 25 glkg higher In the large VT-Iow PEEP group than In the small VT-hlgh PEEP group (p< 0.05). Venous admixture (ava/at) was similarly greater in the large VT-Iow PEEP group (49.8 versus 23.5%)(p< 0.05). We conclude that small VT-hlgh PEEP is a better mode of ventilating acute lung Injury than large VT-Iow PEEP because edema accumulation Is less and venous admixture Is less. These advantages did not result from differences In Pel, end-Inspiratory lung volume, or preload (Ppwtm).