To verify the potential involvement of the age-dependent modifications of EC-SOD activity in the impairment of plasma NO availability with advancing age, 40 healthy men divided into 4 age groups for the purpose of comparison (young: 27.4 +/- 1.5 years; middle: 50.8 +/- 2.2, years; old: 70.0 +/- 1.8 years; very old: 86.1 +/- 1.1 years) were enrolled in this study. Plasma samples were used for measurements of the stable end-product nitrite/nitrate (NOx), as an expression of NO availability, EC-SOD activity, thiobarbituric acid reactive substances (TBARS) as a marker of lipid peroxidation, low density lipoprotein (LDL) copper-mediated oxidation in vitro and total antioxidant capacity (TEAC). Our results indicated a significant age-related progressive decrease of plasma NOx content and EC-SOD activity and their values were positively correlated (r = 0.713, p < 0.001). Increased TBARS amount together with reduced lag time for in vitro oxidation of LDL and decreased content of TEAC were observed with advancing age. Finally, EC-SOD values were negatively correlated with plasma TBARS values (r = -0.855, p < 0.001). Findings of the present study suggest that the decrease of antioxidant defence strategies play a primary role by compromising NO availability in normally aged individuals, particularly through a progressive decrease of EC-SOD activity.