This study reports the results of a 6-month, open-label multicenter study of the efficacy and tolerability of lovastatin, a 3-hydroxy-3-methylglutaryl co-enzyme A (HMG CoA) reductase inhibitor, in the management of nonfamilial primary hypercholesterolemia. The study enrolled 489 patients with elevated total serum cholesterol levels, whose lipids were not controlled sufficiently by diet. There was good representation of gender (48.3% women and 51.7% men), age (mean 57, range 25 to 83) and hypertension status (55.4% normotensive and 43.6% hypertensive) in the sample. Within 1 month of lovastatin therapy, total cholesterol was reduced 19% (from a mean of 269 to 217 mg/dl, low-density lipoprotein (LDL) cholesterol was reduced 27% (191 to 140 mg/dl), high-density lipoprotein (HDL) cholesterol increased 6% (42.6 to 45.1 mg/dl), the ratio of total cholesterol to HDL was reduced 24% (6.7 to 5.1) and the ratio of LDL to HDL was reduced 30% (4.7 to 3.3). These results were consistent across age group, gender and hypertension status, and were maintained for a period of 6 months of therapy. Lovastatin was generally well tolerated. Of the 489 patients enrolled, 449 (92%) completed 6 months of therapy. Only 21 (4%) withdrew because of adverse experience regardless of cause. None of the few serious adverse experiences (e.g., myocardial infarction) could be attributed to the drug. Abnormal laboratory values during the 6 months of therapy were within expectations. Seventy-four patients had at least 1 abnormal value during 6 months of treatment. Of these, 42 had at least 1 mild to moderate creatine phosphokinase elevation during this period. Only 1 patient had an adverse change on ophthalmologic examination: a posterior subcapsular opacity in both eyes just visible on 6-month examination.