Pravastatin is a new drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the key enzyme in cholesterol synthesis. It prevents mevalonate synthesis, thus reducing cholesterol. Pravastatin also stimulates the expression of LDL receptors, leading to an activation of this specific pathway of LDL catabolism. Gemfibrozil is a fibrate drug. Although the mechanism of hypolipidemic action of fibrates is not conclusively elucidated, it seems to involve reduction of LDL cholesterol secondary to decreased VLDL production and increased VLDL catabolism. Therefore, it might be hypothesized that combination therapy with both agents could afford greater reduction of cholesterol levels as compared to pravastatin alone. This study compared the efficacy and safety of pravastatin in monotherapy or in combination with gemfibrozil in the treatment of primary hypercholesterolemia with moderate hypertriglyceridemia. Thirty-eight subjects (aged 57 +/- 15 years, 25 M and 13 F) with baseline cholesterol levels > 220 mg/dl, were included in the study. Serum triglyceride levels were greater than 170 mg/dl and lower than 250 mg/dl. All patients initially followed 4 weeks of hypolipidemic diet. The patients were there assigned to receive either 20 mg once a day of pravastatin alone (n 13) or 20 mg of pravastatin in association with 600 mg of gemfibrozil daily (n 11). Fourteen additional patient, treated with diet only, served as a control group. The treatment plan provided 18 months of active treatment with clinical and laboratory controls every month. Both groups of treated patients showed a reduction of total and LDL-cholesterol levels. The HDL-cholesterol levels increased significantly both with pravastatin and with gemfibrozil.(ABSTRACT TRUNCATED AT 250 WORDS)