The primary goal of this study is to determine if uremic pulmonary edema is the result of an increase in lung vascular permeability or an increase in lung microvascular pressure or both. Uremia will be induced in awake sheep by a variety of methods including chronic reinfusion of urine into the circulation, bilateral nephrectomy, and reduction of renal mass. All sheep will be prepared with vascular catheters and a chronic lung lymphatic fistula so that the composition and flow of lymph from the lungs can be determined. Alterations in lung vascular permeability will be determined by comparing the observed flow of lymph and concentration of proteins in the lymph during uremia to the changes caused by mechanical increases in microvascular pressure. Left atrial and ventricular pressure and cardiac output will be monitored to assess changes in myocardial contractility during uremia. The role of the renal tissue in the pathogenesis of uremic pulmonary edema will be investigated by comparing the lung's responses to uremia in sheep with and without renal tissue present. To determine if the lung's response is mediated by a specific circulating toxin, the ability of uremic plasma and specific uremic toxins (urea, creatinine, methylguanidine, guanidinosuccinic acid) to induce uremic pulmonary edema in sheep will be investigated. Uremic pneumonia and edema contribute to the morbidity and mortality of patients with renal failure. These studies should help identify the mechanisms causing uremic pulmonary edema and lead to methods to modify or prevent its development.