Transfer from a low cholesterol commercial diet to a high cholesterol diet, containing 2% (wt/wt) cholesterol and 0.5% cholate, caused an increase in serum cholesterol from about 2.5 mmol/L in two inbred rat strains to 5 mmol/L in the hyporesponsive strain and to 20 mmol/L in the hyperresponsive strain. In both strains the excess of cholesterol in the serum was exclusively located in the very low density lipoproteins. Cholesterol feeding caused a sevenfold increase in the amount of cholesterol in the liver, the increase tending to be greater in the hyporesponders. On the commercial diet, the decay of specific radioactivity of serum cholesterol after the intravenous administration of labeled cholesterol was faster in the hyporesponsive rats. The rate of fecal excretion of radioactive bile acids on this diet was higher in the hyporesponders when compared with the hyperresponders, whereas there was no strain difference with regard to the output of fecal neutral steroids. Sterol balance data showed that whole-body cholesterol synthesis on the low cholesterol diet was about twofold higher in the hypo- than in the hyperresponders. When fed the high cholesterol diet the half-life in the serum of injected radioactive cholesterol was about six times shorter in the hyporesponders. In absolute amounts, the hypo- and hyperresponders excreted similar amounts of endogenous (radioactive) bile acids and fecal steroids with the feces on this diet.