These studies concern the basis of reduced binding of small ligands by serum proteins in patients with advanced renal failure. An extract of uremic sera contains 3 or more binding inhibitors, which appear to be organic acids. Using sequential chromatography the inhibitors will be obtained in pure form and chemically identified. Using the isolated perfused rat kidney we will determine the mode of excretion of these inhibitors, whether competition exists among the inhibitors for excretion and between the inhibitors and commonly used drugs, which are largely excreted by the kidneys. Once methods for determining each inhibitor have been developed, the determinants of their production and excretion in humans will be studied. Finally, the nature of their interaction with the main serum transport protein, albumin, will be determined.