The concentrations of total serum cholesterol and triglycerides and serum HDL cholesterol, triglycerides and apoproteins A-I and A-II were measured in 119 men after 4 years of active participation in a multifactorial primary prevention trial of coronary heart disease. No difference was observed in total serum cholesterol, triglycerides, HDL lipids or apoproteins between the control subjects without medication and the men treated with antihypertensive drugs (beta-blockers alone or in combination with thiazides). The concentration of HDL cholesterol was significantly lower and that of apoprotein A-II significantly higher in the individuals treated with clofibrate than in the controls. On the other hand, the levels of both HDL cholesterol and apoprotein A-I were lower in the men treated with probucol than in the controls, whereas that of A-II was within the control limits. The ratio HDL cholesterol/apoprotein A-I was subnormal in all 3 groups treated with lipid-lowering drugs, as if the treatment had lowered the cholesterol saturation of the HDL fraction. The levels of HDL cholesterol and apoprotein A-I were negatively correlated with the length of the treatment in subjects treated with probucol but not in the other groups. These results suggest that in long-term use, probucol and possibly clofibrate lower both the concentration and the cholesterol/apoprotein ratio of the HDL fraction.