The perfluorochemical exchange transfused rat was used to examine whether the interaction of plasma proteins with the luminal surface of endothelial cells effects the permeability of pulmonary capillaries. Ultrastructural immunocytochemical techniques were used to localize albumin and IgG. The results indicated that the presence of plasma proteins localized solely within the glycocalyx was sufficient to render the underlying pulmonary capillary endothelium as impermeable to intravenously injected native ferritin (pI 4.7) as that of nonexchange transfused control rats. In further experiments it was observed that the removal of circulating plasma proteins by exchange transfusion resulted in the unmasking of anionic sites on the glycocalyx. This was determined by morphometry by counting the number of intravenously injected cationized ferritin particles (pI 8.5) bound to the luminal surface of the endothelium. There was no statistically significant difference in the amount of binding to the thick and thin sides of the capillaries. These observations support the fiber matrix model of capillary permeability as formulated by Curry and Michel.