1.Cholic acid feeding strongly depresses the activity of the rate limiting enzyme of cholesterol synthesis in liver 3-hydroxy-3-methylglutaryl CoA reductase. Experiments were undertaken to decide between (a) a direct influence of the bile acid itself in liver or (b) an indirect effect of the bile acid by improving the intestinal resorption of cholesterol, which itself then would depress the activity of hepatic 3-hydroxy-3-methylglutaryl CoA reductase.2. For this purpose lymph fistula rats were fed with cholic acid. Compared with the control animals, which did not obtain cholic acid, the experimental groups showed strong depression of 3-hydroxy-3-methylglutaryl CoA reductase activity. This was only observed with animals killed during the dark period, i.e. when the rhythmically changing activity of the enzyme was high.3. A partial depression of the enzyme by fasting can be excluded, because animals fed with or without cholic acid, respectively, ingest the same amount of food.