The specific aim of the proposed studies is to provide more detailed information on the nature of metabolic reactions involved in the conversion of cholesterol to bile acids in man. The experiments are carried out in patients with complete biliary diversion, normal subjects with an intact enterohepatic circulation, and patients with disordered bile acid metabolism (liver disease, biliary atresia). The general approach is to administer one or more 3H or 14C labeled bile acid intermediates and determine the rapidity and efficiency of their conversion to cholic acid and chenodeoxycholic acid. Patients with complete biliary diversion represent an excellent model to study the efficiency of conversion of various intermediates to bile acids since: a) quantitative data can be obtained, b) several intermediates can be administered on several consecutive days, and c) specific activity time curves of cholic acid and chenodeoxycholic acid can be compared. The additional experiments in subjects with intact enterohepatic circulation will provide data obtained under existing physiologic conditions. It is hoped that the findings accumulated from these studies will allow for more definitive delineation of the major and minor degradative pathways of cholesterol metabolism to bile acids. No regulatory concept of cholesterol metabolism in man can be fully understood until this information is available in man. The potential findings of the proposed studies may have important implications in elucidating the abnormalities of lipid metabolism in man.