Simvastatin (synvinolin MK-733) is a potent inhibitor of 3-HMG-CoA-reductase, the key enzyme for cholesterol biosynthesis. To investigate the efficiency and safety of this new drug on a long term basis, simvastatin was administered for 3 years to ten patients with type II hyperlipoproteinemia. Daily dosages were 20 or 40 mg. The drug therapy produced a significant reduction in serum levels of total cholesterol (19-34%), LDL-cholesterol (26-44%) and Apo B (19-33%). Triglycerides decreased moderately (2-23%) while HDL-cholesterol and Apo A1 changed only slightly (-3 to 6% and 5-13% respectively). Simvastatin was well tolerated. No consistent adverse clinical or biochemical effects were observed during the three-year therapy. The results indicate that simvastatin is a promising new therapy for high risk hypocholesterolemic patients.