Although Acute Lung Injury (ALI) has been well studied in adults, the clinical and biological mechanisms of ALI in pediatric patients have not been well explored in prospective studies. Therefore, we began a prospective study of pediatric ALI in the Pediatric Intensive Care Units of both a major university medical center and a large, inner city children's hospital. The overall objective is to identify biological and clinical markers that will have both prognostic and pathogenetic significance. Initial analysis of the data collected on 158 patients indicates that pediatric ALI is remarkably different from adult ALI. For example, mortality is significantly lower in pediatric patients (22 percent) compared to adult studies (40-55 percent). Unlike adult patients, the severity of initial oxygenation defect identifies which pediatric patients have a higher risk of non- survival. In order to study the mechanism of pediatric ALI, serum has been collected on a majority of patients within the first 48 hours of onset of ALI. Our primary hypothesis is that the severity of lung endothelial and lung epithelial injury will be greater in patients with more severe respiratory failure (duration of mechanical ventilation) and greater overall mortality. Endothelial injury will be assessed by measurement of von Willebrand Factor antigen and alveolar epithelial injury by measurement of soluble Intercellular Adhesion Molecule-1 (sICAM- 1) and a recently identified alveolar epithelial Type-1 cell antigen. The relationship of these markers to the clinical course and outcome of pediatric ALI will be explored in 350 patients. This data will provide the first comprehensive prospective study of pediatric ALI using a standard, internationally accepted definition with a combination of epidemiological and biological markers of acute lung injury.