Cigarette smoking has been shown to be a major risk factor for cardiovascular disease, lung cancer, and respiratory diseases. Due to its high content of oxidants, the cigarette smoke is bound to cause a prooxidant/antioxidant imbalance in the blood plasma and tissues of smokers. The study groups were selected from an apparently healthy population living in urban areas, comprising 200 subjects aged 18 to 80 years, half of whom were smokers. In smokers aged 18 to 45 years, the changes of the plasma prooxidant parameters (i.e., lipid peroxides, leukocyte activation, and the antioxidant ones [thiol concentration, total antioxidant capacity]) were not significantly different from those of the age-matched controls, whereas in the 46 to 80 age group they were. In smokers, both antioxidant erythrocyte enzymes, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), exhibited increased activity in the 18 to 45 age group and decreased activity in the 46 to 80 age group. The differences in enzyme activity between the smoking and nonsmoking groups were highly significant for SOD in all ages, whereas for GSH-Px the difference in activity was significant only in the case of older smokers. These findings would suggest that a process of adaptation takes place in younger smokers, in whom the antioxidant systems are able to counteract the oxidant factors, while in older smokers this process is no longer occurring and the plasma and tissues are under permanent oxidative stress. Our results clearly demonstrated that a prooxidant/antioxidant imbalance exists in the blood of smokers, and the determination of leukocytes stimulation index may be a useful and simple way of assessing the oxidative stress status of these individuals. A hypothesis regarding a possible mechanism linking cigarette smoking to the development of coronary heart disease is presented.