The specific aim of this retrospective, observational study was to assess safety and efficacy of long-term (21 months/patient), open-label, gemfibrozil-lovastatin treatment in 80 patients with primary mixed hyperlipidemia (68% of whom had atherosclerotic vascular disease). Because ideal lipid targets were not reached (low-density lipoprotein (LDL) cholesterol less than 130 mg/dl, high-density lipoprotein (HDL) cholesterol greater than 35 mg/dl, or total cholesterol/HDL cholesterol less than 4.5 mg/dl) with diet plus a single drug, gemfibrozil (1.2 g/day)-lovastatin (primarily 20 or 40 mg) treatment was given. Follow-up visits were scheduled with 2-drug therapy every 6 to 8 weeks, an average of 10.3 visits per patient, with 741 batteries of 6 liver function tests and 714 creatine phosphokinase levels measured. Only 1 of the 4,446 liver function tests (0.02%), a gamma glutamyl transferase, was greater than or equal to 3 times the upper normal limit. Of the 714 creatine phosphokinase levels, 9% were high; only 1 (0.1%) was greater than or equal to 3 times the upper normal limit. With 2-drug therapy, mean total cholesterol decreased 22% from 255 to 200 mg/dl, triglyceride levels decreased 35% from 236 to 154 mg/dl, LDL cholesterol decreased 26% from 176 to 131 mg/dl, and the total cholesterol/HDL cholesterol ratio decreased 24% from 7.1 to 5.4, all p less than or equal to 0.0001. Myositis, attributable to the drug combination and symptomatic enough to discontinue it, occurred in 3% of patients, and in 1% with concurrent high creatine phosphokinase (769 U/liter); no patients had rhabdomyolysis or myoglobinuria.(ABSTRACT TRUNCATED AT 250 WORDS)