Paraoxonase-1 (PON-1), an HDL-associated enzyme has been shown to possess antioxidant/anti-inflammatory properties and protect against atherogenesis. The aim of the study was to explore the association of PON-1, with lipids, antioxidant-vitamins and lifestyle in male subjects with and without angiographically documented coronary artery disease (CAD) and in healthy volunteers. PON-1 activity was measured spectrophotometrically using phenyl acetate as substrate. PON-1 and HDL-Cholesterol were significantly lower and lipid peroxides and triglycerides were higher in CAD patients than in normal coronary and control subjects. PON-1 activity showed positive association with HDL-C and inverse relation with lipid peroxides and no association with antioxidant vitamins in healthy subjects. Smoking habit, alcohol intake and diabetes mellitus did not seem to influence PON-1 activity. Serum levels of PON-1 and HDL-C showed inverse association with the presence of CAD but are not related to the severity of disease in terms of number of diseased vessels. Interventional means by diet/drugs to enhance PON-1 activity may contribute to attenuation of atherosclerosis.