The long-term effects (66 weeks) of simvastatin (40 mg in one or two doses per day), an inhibitor of HMG CoA-reductase, were evaluated in 12 patients with familial dysbetalipoproteinaemia (type III hyperlipoproteinaemia). Simvastatin had a persistent hypolipidaemic effect; the mean reduction in serum cholesterol was 36-51%, and the mean reduction in serum triglycerides was 32-55%. The decrease in serum lipids was caused by a decline in VLDL-cholesterol and LDL-cholesterol levels; the mean ratio between VLDL-cholesterol and serum triglycerides decreased significantly from 1.06 to 0.73. There was no significant difference between the once-a-day and twice-a-day regimens. Simvastatin was well tolerated; no serious side-effects were observed. These data demonstrate the usefulness of simvastatin in the therapy of familial dysbetalipoproteinaemia.