Simvastatin (MK 733), a new competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, given in daily doses of 20 mg and 40 mg for 104 weeks, has been shown to lower the serum total cholesterol and low density lipoprotein cholesterol level by more than 30% and the serum apoprotein B level by 20% in 19 adult patients with heterozygous familial hypercholesterolemia. A slight but non-significant increase of high density lipoprotein cholesterol levels was shown throughout the trial with significant elevation of the serum apoproteins AI and AII only observed at week 52. Mild and transient clinical or biochemical (increases of creatine phosphokinase and transaminases) side effects, observed in some patients, did not necessitate the withdrawal of the medication. Full ophthalmological examinations did not reveal ocular disturbances, particularly no apparent increase of lens opacities, during the trial. Simvastatin seems to be an effective and safe drug as monotherapy in the treatment of heterozygous familial hypercholesterolemia.