266 patients with primary hypercholesterolaemia were followed for 48 weeks at 27 different centres to evaluate the safety, tolerability and effect on plasma lipids of lovastatin ranging from 20 to 80 mg/day. Mean change from baseline after 12 weeks of treatment with lovastatin was -34% (CI:33-35) for total cholesterol, -42% (CI:40-43) for LDL-cholesterol, +14% (CI:12-17) for HDL-cholesterol and -14% (CI:10-18) for triglycerides. Combination therapy with cholestyramine (8-24 g/day) was optional, and was started in 89 patients from week 13. At week 48 only 25% of all patients had obtained the second objective of the study: a total cholesterol value below 5.2 mmol/l. At the same time 60% of all patients had a total cholesterol below 6.2 mmol/l. Four patients dropped out of the study owing to adverse clinical experience. Only three of these events were probably related to lovastatin. Six patients were withdrawn because of adverse laboratory experiences. One patient showed clinical signs of myositis and increase of CK. In severe primary hypercholesterolaemia combination therapy with lovastatin and a resin such as cholestyramine is required to obtain total cholesterol values below 5.2 mmol/l.