Edema is a common clinical condition in heart failure, nephrotic syndrome and other pathological states. In many tissues, gross edema causes functional abnormalities. Within limits, powerful compensatory mechanisms operating at microvascular, interstitial and lymphatic levels serve to protect the tissues against excessive accumulation of fluid in the interstitium. The objective of the proposed research is to examine the role of each individual compensatory mechanism in preventing edema formation. To achieve our goal, we propose 4 series of experimental studies. The first focuses on the regulation of transcapillary fluid balance in muscle, liver and heart. The physicochemical properties of the interstitial gel is the subject of the second series. The third series of experiments is designed to characterize the pumping action of muscular lymphotics, utilizing quantitative microscopic techniques. In the final series, we examine the effects of long-lasting edema on the interstitium and lymphatic pump. From these studies, we hope to gain new insights into the mechanisms, prevention and treatment of edema formation.