Repeated lung inflation with very high tidal volumes (VT) is associated with the production of permeability pulmonary edema in animal models using previously normal lungs. We studied the effect of mechanical ventilation, at VT values approaching those used clinically, on lung weight gain (lung water) in salt-perfused rabbit lungs diffusely injured by the administration of oleic acid. Lungs ventilated at a VT of 18 ml/kg gained significantly more weight at 30 through 90 min than did lungs ventilated at 6 ml/kg. These differences in weight gain were not associated with differences in the evolution of thromboxane B2 in the perfusate. The impact of VT on lung water and outcome in patients with lung injury deserves further study.