The role of low density lipoprotein (LDL) cholesterol as well as of that transported by other lipoproteins, such as high density lipoprotein (HDL), in the pathogenesis of atherosclerotic disease has been pointed out by several studies. Nevertheless, recent researchers have suggested that cholesterol transported by other lipoproteins, e.g. very low density lipoproteins (VLDL), could play a role in the atherosclerotic disease. Consequently the evaluation of non-HDL cholesterol could provide a more significant index of the atherosclerotic risk in hyperlipoproteinemic patients. Clinical investigations have shown that the competitive inhibitors of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase are very effective to decrease LDL-Cholesterol serum concentration, but their effect on the cholesterol of other lipoproteins is not well known. The effect of 6 months of treatment with simvastatin (20 mg/day) on lipoproteinemic pattern was retrospectively studied in 102 patients with primary hypercholesterolemia. A significant reduction in serum levels of non-HDL-cholesterol and VLDL-cholesterol together with the expected reduction of total cholesterol, apolipoprotein B 100, LDL-cholesterol and an increase of HDL cholesterol were observed. Triglyceride serum behaviour was inversely correlated with HDL cholesterol during the study. Our data suggest that simvastatin can reduce the cholesterol of all potentially atherogenetic lipoproteins and could improve the inverse cholesterol transport system expressed by the HDL cholesterol transport system expressed by the HDL cholesterol increment by a mechanism probably dependent on normalisation of the plasma lipoprotein pattern in atherosclerotic disease.