Abstract A comparison has been made of the effects of the ileal exclusion operation and the administration of cholestyramine in 9 patients with hypercholesterolemia. In both cases the enterohepatic circulation of bile acids was interrupted by interference with their reabsorption. Second, there was an increased conversion of cholesterol into bile acids along with an enhanced synthesis of cholesterol; the latter occurred apparently in both the liver and intestinal tract. A fall in plasma cholesterol was found in most patients, but in 2 patients with severe hypercholesterolemia, both cholestyramine and ileal exclusion produced a slight rise in plasma levels. While our data show that bile acids exert a direct inhibitory effect on conversion of cholesterol into bile acids, a clear definition of the influence of bile acids on cholesterol synthesis is more difficult. The present data prove that bile acids directly inhibit cholesterol synthesis in the intestinal mucosa in man. Nevertheless, cholesterol synthesis in the liver may be regulated by the enterohepatic pools of bile acids, either through their control of cholesterol absorption or by direct action in the liver; presently available information permits no choice between these 2 possibilities. Our findings indicate that there are no essential differences in the actions of ileal exclusion and cholestyramine on cholesterol metabolism in man. Both interventions are effective in lowering plasma cholesterol concentrations in most patients except in those with the most severe forms of hypercholesterolemia.