This randomized, blind study measured changes in serum lipid and apolipoprotein concentrations in 16 men consuming 39 +/- 1% of energy (en%) as fat either from safflower- or canola-oil-based diets for 8 wk. Initially, the men were stabilized for 3 wk on a typical American (baseline) diet. Compared with baseline, the vegetable-oil-based diets reduced serum total cholesterol 9-15% (P less than 0.002), low-density-lipoprotein (LDL)-cholesterol 12-20% (P less than 0.002), and apolipoprotein B-100 21-24% (P less than 0.001). There were no significant changes from baseline to the end of the study in serum triglycerides, total high-density-lipoprotein (HDL) cholesterol, HDL3 cholesterol, HDL2 cholesterol, or apolipoprotein A-I. These data suggest that even if total fat intake remains at 39-40 en%, many men show lowered LDL cholesterol if saturated fatty acid intake is minimized and that diets high in polyunsaturated fatty acids do not necessarily lower HDL-cholesterol concentrations.