Interleukin-1 (IL-1) and neutrophils are increased in lungs of patients with the acute respiratory distress syndrome (ARDS). We found that rats given IL-1 intratracheally rapidly developed lung neutrophil accumulation and a neutrophil-dependent acute edematous lung leak. Lung leak was associated with increased lung lavage cytokine-induced chemoattractant (CINC) levels and increased oxidative stress that was manifested by increased exhaled H2O2 levels and increased lung oxidized glutathione levels. IL-1-induced lung leak was decreased by treatment with superoxide dismutase (SOD), dimethylsulfoxide (DMSO), supercritical fluid-aerosolized vitamin E, interleukin-1-receptor antagonist (IL-1ra), or liposome-associated PGE1 (Lip-PGE1). Importantly, Lip-PGE1 treatment also reduced ventilator dependence in a small clinical study of ARDS patients. Another series of investigations revealed that IL-1 pretreatment could prevent lung leak in rats given IL-1 intratracheally. These findings point to the possible dual effects of IL-1 with respect to the development of acute lung injury.