The effects of transfusion of whole blood clot emboli and aged citrated platelet-poor plasma on pulmonary capillary permeability were investigated in anesthetized sheep by continuous collection of pulmonary lymph. Changes in lymph flow and lymph to plasma ratios [C(L)/C(P)] for albumin and globulin were utilized to detect changes in permeability. Infusion of 0.5 cc/kg of finely (≤1 mm) diced autologous whole blood clot resulted in a 170% increase in lymph flow over control with no change in C(L)/C(P) for albumin or globulin. Infusion of 1 cc/kg of autologous clot increased lymph flow 180% over control and increased C(L)/C(P) for albumin and globulin. Infusion of homologous platelet-poor plasma caused greater increases in lymph flow without changes in C(L)/C(P). Changes in each of these three groups were consistent with increased permeability. Balloon occlusion of one main pulmonary artery was induced without a fall in cardiac output and resulted in no change in lymph flow or C(L)/C(P) despite a rise in pulmonary vascular resistance (PVR). Femoral arteriovenous fistulas were created to increase cardiac output, but no change in lymph flow or C(L)/C(P) occurred. The results in these latter two experiments suggest that increased perfusion per unit lung capillary bed or increased PVR were not primarily responsible for the changes observed in the emboli-treated and plasma-infused animals. Since both emboli and aged platelet-poor plasma increased pulmonary capillary permeability, the permeability increasing factor appears to be humoral in origin. Similar humoral factors may be important in the pathogenesis of the adult respiratory distress syndrome in man.