Lovastatin, a potent inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase, was investigated in a placebo-controlled trial of 26 primary hypercholesterolemic subjects. Drug dosage varied from 20 to 40 mg/d in a single dose on a 12 weeks treatment period. Average plasma cholesterol reduction levels were 17 and 31%, and LDL-cholesterol 24 and 41% on 20 and 40 mg/d respectively. High-density lipoprotein and triglycerides levels did not change significantly. Similar mean decreases in total plasma cholesterol and LDL-cholesterol levels were observed in hypercholesterolemics irrespectively of being of familial origin or not. No serious clinical and laboratory abnormalities were observed. In this study, lovastatin was a well tolerated and effective agent for the treatment of non familial and heterozygous familial hypercholesterolemia.