These various observations suggest that the intestinal-hepatic axis plays a key role in the regulation of cholesterol balance in the whole animal and the circulating levels of LDL-cholesterol. Nearly all sterol which enters or leaves the body must do so through the intestine and liver. Changes in the rate of entry or exit of cholesterol (or bile acids) from the animal are met by appropriate reciprocal changes in the rates of cholesterol synthesis in these two organs. As long as these adaptive changes in synthesis are adequate to meet the changing needs for cholesterol in the animal, the rates of receptor-mediated LDL degradation by the liver and intestine remain essentially unchanged as does the plasma LDL-cholesterol concentration. Only when the changes in cholesterol synthesis are inadequate to meet the changing sterol needs (or are blocked by drug administration (22] does the liver increase its rate of receptor-mediated LDL uptake which, in turn, results in significant alterations in circulating plasma LDL-cholesterol levels.