This proposal is concerned with the role of albumin in regulating water balance in the normal lung and as a primary factor in the cause and therapy of pulmonary edema. A combination of independent techniques (radioisotopes, electrophoresis, and immunoassay) will be used to establish the concentration of albumin in the pulmonary interstitial space and to confirm the Starling forces determining water content. Pulmonary capillary permeability will be measured using multiple indicator dilution techniques, together with a computer deconvolution analysis in animals, human volunteers, and patients and in computer simulations. From these data, together with kinetic analysis of steady state albumin exchange, a model of the water and albumin exchange will be constructed to include both diffusive and convective exchange across the pulmonary capillary, as well as lymphatic flow. The heterogeneity of albumin distribution in the whole body will be established and the dynamics of extravascular/intravascular exchange of albumin investigated in stress states. Finally, the influence of therapy (diuretics, albumin, steroids, etc.) on whole body versus pulmonary albumin distribution will be evaluated.