This study was carried out to assess the efficacy and safety of combined therapy with pravastatin and gemfibrozil in patients with severe refractory familial combined hyperlipidaemia.26 patients (18 men and 8 women) with a mean age of 50 years (range 32 to 65 years) were included in the study. Patients with secondary forms of dyslipoproteinaemia were excluded. All patients had been following a phase II American Heart Association hypolipidaemic diet plus placebo for 1 month. Beginning at month 0, the patients received 4 months of combined treatment with a fixed dosage of gemfibrozil 1200 mg/day (divided into 2 equal doses), and pravastatin 20 mg/day. The dosage of pravastatin was increased to 40 mg/day after 1 month.At months -1, 0, 1, 2, 3 and 4 the following parameters were measured: total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), and apoproteins B and A-I. In the 17 patients free of coronary heart disease (CHD) at baseline, the effect of treatment on the risk of myocardial infarction (MI) was calculated.Before treatment initiation, the mean values (± SD) of the measured parameters were: TC = 309 ± 23 mg/dl, TG = 253 ± 35 mg/dl, LDL-C = 221 ± 21 mg/dl, VLDL-C = 49 ± 7 mg/dl, HDL-C = 34 ± 5 mg/dl, apoprotein B = 170 ± 10 mg/dl and apoprotein A-I = 118 ± 11 mg/dl. After 4 months of combined treatment the following percentage changes were recorded: TC-31%, LDL-C -35%, VLDL-C-51%, HDL-C+20%, TG-47%, apoprotein B-34%, apoprotein A-I+11%, LDL-C to HDL-C ratio -45%, and apoprotein B to A-I ratio -41%. The relative risk of MI was reduced by 58%. All changes were significant (p < 0.001).No patient was withdrawn from the study because of treatment-induced adverse effects. Five patients exhibited a moderate transient serum enzyme elevation: 2 in creatinine kinase and 3 in transaminase. Myopathy or rhabdomyolysis, major gastrointestinal symptoms, deterioration of renal function, or insomnia were not recorded in any patients.Combined treatment with gemfibrozil and pravastatin is safe and effective, but should be administered only in selected patients with severe combined hyperlipidaemia.