Zondek (1) as early as 1934 demonstrated that enzymes of the liver destroyed the biological activity of the estrogens. Since then both in tivo and in vitro studies have provided much evidence to show that the liver is the organ primarily responsible for the catabolism of the steroid hormones: estrogens, androgens, progesterone, and the corticosteroids (2). However, not until the development of improved methods for measurement of certain of the adrenocortical steroids and their metabolites, and the availability of labeled radioactive cortisol, corticosterone, and aldosterone has it been possible accurately to evaluate the influence of liver disease on the rate of degradation and synthesis of the steroids in man. The studies here reported are based on the use of certain of these newer techniques.On incubation with rat liver tissue, cortisol and cortisone are rapidly metabolized, but only very slowly with other tissues (3-5). Perfusion studies have demonstrated a very rapid metabolism of the steroids by the liver but not by other organs (6-8). Hechter, Frank, Caspi and Frank (9) found that the major portion of the cortisone and cortisol administered into the portal vein in dogs was not recovered as unaltered steroid from the hepatic venous blood. Bradlow, Dobriner and Gallagher (10) found that 70 per cent of a dose of tritium-labeled cortisone administered to mice was found in the liver within five minutes after intravenous administration. Administered cortisol also disappears rapidly from the circulation in rats (11), and this rapid metabolism can be prevented by hepatectomy but not by nephrectomy (12).The liver in man has a high capacity for metabolizing the circulating blood cortisol, as demonstrated by the fact that the level of 17-hydroxycorticosteroids in the hepatic vein blood is lower than the level in the arterial blood (13,14). Adrenocortical steroids administered intravenously