The effect of treatment with simvastatin, a new HMG-CoA reductase inhibitor, has been investigated in 27 patients with primary hypercholesterolaemia. It produced a significant decrease of cholesterol and phospholipids in plasma, LDL and apolipoprotein B-containing lipoproteins. Plasma apolipoproteins B, C-III and E were also significantly lowered. The concentration of lipoprotein particles recognized by monoclonal antibodies (BL3, BL5 and BL7), associated with atherosclerotic disease, was also lowered by the treatment. Lipoproteins LpA-II:A-I were not changed, while LpA-I, which has been suggested to be the protective fraction of the apo A-I-containing lipoproteins, was slightly and inconsistently increased.