Simvastatin, 10-40 mg/d (n = 11), bezafibrate, 600 mg/d (n = 6), and gemfibrozil, 1200 mg/d (n = 5) were administered for 12 weeks after a 4-week placebo period to subjects with initial plasma levels (mg/100 ml. mean +/- SD) of cholesterol (346 +/- 77), and of triglycerides (180 +/- 54). Total LDL-C plasma concentration was lowered 32% by simvastatin and 35% by bezafibrate, but only bezafibrate diminished the triglyceride (41%) and increased HDL-C plasma levels (35%). Plasma lipoprotein fractions obtained by discontinuous gradient ultracentrifugation, namely, VLDL, lighter LDL (LDL-1), heavier LDL (LDL-2) and bulk HDL were chemically analyzed. Simvastatin and bezafibrate significantly diminished the quantity of VLDL and LDL-1 particles, although barely modifying their composition. Neither drug influenced the LDL-2 plasma concentration. Bezafibrate increased the total plasma HDL level little interfering with its chemical composition. Gemfibrozil was the least effective of all drugs but decreased the lipid and protein contents and their ratios in VLDL and LDL-2.