The cholesterol-lowering effect of very-low-fat diets rich in lean beef has previously been shown to be reversed with the addition of beef fat. The aim of this study was to determine the effect on serum lipid levels of the addition of safflower oil or olive oil to a very-low-fat diet rich in lean beef. Subjects were assigned to either the safflower oil or the olive oil group. In the first week the subjects ate their usual diet; in the second and third weeks all subjects ate a very-low-fat (9% of energy) diet rich in lean beef. In the fourth and fifth weeks the fat content of the diet was increased in a stepwise fashion to 20% and 30% of energy, respectively, by substituting safflower oil or olive oil for carbohydrate. Low-density lipoprotein cholesterol (LDL-C) concentrations decreased by 13% to 14%, and high-density lipoprotein cholesterol (HDL-C) concentrations decreased by 20% to 25% in subjects after 2 weeks of the very-low-fat, lean-beef diet. The LDL-C concentrations remained low after the addition of safflower oil or olive oil to the very-low-fat diet. These results indicate that a reduction in saturated fat, not total fat, is required to reduce serum total cholesterol and LDL-C levels. Provided that the total diet is low in saturated fat, these serum lipid responses can be achieved even when the diet is rich in fat-trimmed lean beef.