The central goal of this program is to provide new knowledge concerning the pathophysiology of pulmonary edema, and to utilize this knowledge in the diagnosis, treatment and prevention of pulmonary edema. To achieve this goal, the grant has been organized into three closely related projects during the coming year: one clinical and two experimental projects. A-1: Clinical Studies of Pulmonary Edema: 1) Natural History, Risk Factors, 2) Effects of Treatment: The specific aims of this project are to find a marker, either in the blood or of an abnormality of lung function, that will determine who has sustained diffuse lung injury before the consequences of that injury appear. When such a high risk group can be identified, controlled clinical trials can be carried out to prevent or modify the injury from progressing. B-1: Pathophysiology, Prevention, and Treatment of Increased Permeability Pulmonary Edema: The specific aims of these studies, carried out chiefly in unanesthetized sheep with chronic lymph fistulas, are twofold: first, to define the mechanisms of acute lung injury that result in increased permeability pulmonary edema and second, to discover pharmacologic means of preventing or modifying the consequences of these injuries. B-3: Dynamics of Pleural Fluid and Solute Exchange; with Emphasis on Pleural Effusion: The specific aims of these acute experiments in anesthetized sheep are to examine pleural liquid and protein dynamics in an effort to clarify the relationship between the lungs and the chest wall in the formation and removal of pleural liquid and protein. Both physiologic and anatomic approaches are being utilized.