In the whole animal and in man, cholesterol is acquired either by absorption from the diet or by synthesis in the various organs. While there are marked variations among different animal species, the liver and intestine are generally the most important organs for the synthesis of cholesterol, although recent data indicate that nearly all of the remaining tissues of the body also are capable of significant cholesterol synthesis. Peripheral tissues also acquire cholesterol through the uptake of low density lipoproteins (LDL). However, most LDL are removed from the plasma by the liver, and more than 90% of this clearance process is mediated by the LDL receptor. Hence, the circulating levels of cholesterol carried in LDL are determined primarily by the rate of LDL production and the rate of LDL uptake by the liver. Changes in the rate of entry of cholesterol into the body are compensated for primarily by changes in the rate of cholesterol synthesis in the liver and, to some extent, in the intestine. As long as these changes in synthetic rates can fully compensate for the variations in the rate of cholesterol entry into or exit from the body, the rate of LDL uptake by the liver and the intestine, and the circulating levels of plasma cholesterol, remain essentially constant. When the adaptive changes in cholesterol synthesis are not adequate to meet the changes in cholesterol entry or exit, then the level of LDL receptor activity in the liver may either increase or decrease, resulting in a corresponding lowering or elevation of the circulating plasma LDL-cholesterol levels.