A randomized, double-blind, 12 weeks comparison of Lovastatin and Gemfibrozil in the treatment of patients with primary hypercholesterolemia was performed in 31 patients. After a placebo and diet period (4 weeks), they were assigned to either Lovastatin 20 mg nightly or Gemfibrozil 600 mg twice daily, if their total serum cholesterol was < 300 mg/dl, and to either Lovastatin 40 mg nightly or Gemfibrozil 600 mg/12 if it was > 300 mg/dl. In both cases, the Lovastatin dose was doubled after 6 weeks, if serum cholesterol remained > 200 mg/dl. The dose of Gemfibrozil kept constant. Lovastatin reduced serum cholesterol from 354 +/- 91 mg/dl to 253 +/- 62 mg/dl (p < 0.001), LDL-cholesterol from 277 +/- 104 to 192 +/- 71 mg/dl (p < 0.001) and serum triglyceride level from 125 +/- 66 a 84 +/- 41 mg/dl. The corresponding reductions achieved by Gemfibrozil were: 343 +/- 86 to 290 +/- 72 mg/dl (p < 0.01), 264 +/- 89 to 217 +/- 67 mg/dl (p < 0.05) and 152 +/- 84 to 89 +/- 41 mg/dl (p < 0.001), respectively. Lovastatin therapy caused a 30.6% reduction in total cholesterol level, while Gemfibrozil achieved a 19.47%. There were no significant changes in HDL-cholesterol. Patients had no serious or clinically significant adverse effects. The current data suggest that Lovastatin (an inhibitor of HMG-Coa reductase) may provide one important means for lipid-lowering therapy in patients with primary hypercholesterolemia.