The adult respiratory distress syndrome (ARDS) is a devastating clinical illness characterized by refractory hypoxemia and high-permeability pulmonary edema. Reactive oxygen species may play a key role in the pathogenesis of the acute lung injury. Glutathione is a tripeptide that is able to react with and effectively neutralize oxidants, such as hydrogen peroxide. The present study found that the alveolar epithelial lining fluid of patients with ARDS was deficient in total glutathione compared with that of normal subjects (31.5 +/- 8.4 versus 651.0 +/- 103.1 microM, p = 0.0001) and patients with cardiogenic pulmonary edema (31.5 +/- 8.4 versus 154.1 +/- 52.4 microM, p = 0.001). In addition, a greater percentage of total glutathione was in the oxidized form in patients with ARDS compared with normal subjects (30.6 +/- 6.1 versus 6.4 +/- 2.9%, p = 0.03). This deficiency of reduced glutathione in the alveolar fluid may predispose these patients to enhanced lung cell injury.