Because experimental studies have shown that intact alveolar epithelial fluid transport function is critical for resolution of pulmonary edema and acute lung injury, we measured net alveolar fluid clearance in 79 patients with acute lung injury or the acute respiratory distress syndrome. Pulmonary edema fluid and plasma were sampled serially in the first 4 hours after intubation. Net alveolar fluid clearance was calculated from sequential edema fluid protein measurements. Mean alveolar fluid clearance was 6%/h. Of the patients, 56% had impaired alveolar fluid clearance (< 3%/h), 32% had submaximal clearance (> or = 3%/h, < 14%/h), and 13% had maximal clearance (> or = 14%/h). These findings are contrasted to our recent report of 65 patients with hydrostatic pulmonary edema, in whom mean alveolar fluid clearance was 13%/h; only 25% had impaired clearance whereas 75% had submaximal or maximal clearance (J Appl Physiol 1999;87:1301-1312). Acute lung injury with maximal alveolar fluid clearance were more likely to be female (p = 0.03), and less likely to have sepsis (p = 0.01). Endogenous and exogenous catecholamines did not correlate with alveolar fluid clearance. Patients with maximal alveolar fluid clearance had significantly lower mortality and a shorter duration of mechanical ventilation. In summary, in contrast to hydrostatic pulmonary edema, alveolar fluid clearance in patients with acute lung injury and the acute respiratory distress syndrome is impaired in the majority of patients, and maximal alveolar fluid clearance is associated with better clinical outcomes.