ObjectiveTo test the hypothesis that low concentrations of distal airspace water-soluble antioxidants are associated with acute lung injury.DesignProspective, cohort study.SettingMedical intensive care unit of two tertiary care hospitals.SubjectsSubjects were 29 patients with acute lung injury and 23 normal, healthy, volunteers.InterventionsNone.Measurements and Main ResultsPulmonary edema fluid from subjects with acute lung injury was aspirated immediately after intubation. Compared with the bronchoalveolar lavage from normal subjects (corrected for dilution using urea concentrations), undiluted edema fluid from acute lung injury subjects had significantly lower concentrations of the antioxidants urate (757 ± 232 &mgr;M vs. 328 ± 75 &mgr;M), glutathione (138 ± 25 &mgr;M vs. 7 ± 4 &mgr;M), and ascorbate (85 ± 21 &mgr;M vs. 27 ± 10 &mgr;M).ConclusionsAcute lung injury is associated with decreased concentrations of water-soluble antioxidants in the distal airspaces. In acute lung injury, the distal airspace antioxidants ascorbate, urate, and glutathione may play a role in attenuating lung injury.