A major hindrance to the elucidation of the pathogenesis of the adult respiratory distress syndrome (ARDS) is the lack of an animal model consistent with the clinical course in humans. A continuous intravenous infusion of endotoxin (LPS) over a several day period was used to more closely parallel the clinical setting. Male Sprague-Dawley rats infused with LPS via indwelling right atrial catheters become tachypneic, lethargic and anorectic with a steady loss in body weight. Serial blood gas analyses demonstrate an early respiratory alkalosis followed by increasing acidosis and hypoxia. Lungs demonstrate 1) pulmonary leukoaggregation, 2) interstitial and intraalveolar edema, 3) Type I pneumocyte injury, 4) proliferation of Type II pneumocytes, and 5) thickening of the microvascular walls. Differential neutrophil count in bronchoalveolar lavage (BAL) fluid increased from 1% to a peak of 59.1% +/- 3.0% and protein content was elevated. A prolonged infusion of LPS in the rat produces a lung injury which mimics many of the pathophysiologic and histologic features associated with sepsis-induced ARDS in humans.