It is now well established that diets rich in saturated fatty acids lead to high levels of serum cholesterol, whereas diets rich in unsaturated fatty acids tend to be associated with lower levels. The mechanism by which these changes in serum cholesterol are induced by dietary fat is not known. One possible explanation for these effects would be either inhibition of cholesterol biosynthesis by unsaturated fats or stimulation of synthesis by saturated fats. The effects on synthesis, if any, could, in turn, be either the result of a direct action of the dietary fat on the biosynthetic system or of a secondary adjustment to any change in the rate of oxidation and excretion of cholesterol and its metabolites. Alternatively, changes in dietary fat might not affect the turnover rate, but cause a shift of part of the serum cholesterol pool, either from or into tissue compartments.Finally, the changes in serum cholesterol might reflect a primary effect not on sterol metabolism per se, but on the metabolism of lipoproteins, direct or mediated through effects on the metabolism of one or several of the moieties making up the macromolecule. These might act singly or in combination.In the present studies we have administered cholesterol-4-14C to subjects fed liquid formula diets containing saturated or unsaturated fat and subsequently measured the specific radioactivity of plasma cholesterol as a function of time. Simultaneously, the fecal excretion of sterol and bile acid was measured by a radioactivity balance method.