Plasma alpha-tocopherol, ascorbate, retinol, uric acid, and lipid peroxides were investigated in 39 male smokers and 64 male non-smokers. The average level of plasma alpha-tocopherol of 35-45-year-old smokers (1.74+/-0.49 microg/mg total lipid) was significantly lower than that of age-matched non-smokers (2.55+/-0.88 microg/mg total lipid, P = 0.032). Similarly, the plasma alpha-tocopherol of smokers aged above 45 (1.66+/-0.29 microg/mg total lipid) was lower than that of the age-matched non-smokers (2.38+/-1.26 microg/mg total lipid, P = 0.014). However, no difference in plasma level of alpha-tocopherol was found between smokers and non-smokers below the age of 35. The average concentration of ascorbate in plasma was significantly decreased only in those smokers older than 45 (0.33+/-0.16 mg/dl vs non-smokers 0.53+/-0.19 mg/dl, P = 0.003). The average level of lipid peroxides (measured as malondialdehyde,MDA) in the plasma of smokers (2.77+/-0.51 nmol/ml) was higher than that of non-smokers (2.35+/-0.21 nmol/ml) aged above 45 (P = 0.034). No differences in the plasma levels of uric acid and retinol were noted between smokers and non-smokers in all age groups. Using partial correlation analysis under age control, we found that the plasma level of alpha-tocopherol was negatively correlated with the plasma level of MDA (r = -0.523, P = 0.038). In contrast, the plasma level of ascorbate was only weakly correlated with the plasma level of MDA (r = -0.341, P = 0.094). Moreover, we found a negative correlation between the plasma level of alpha-tocopherol and smoking index (r = -0.414, P = 0.006) under age control, but there was no correlation between plasma level of ascorbate and smoking index (r=0.221, P = 0.193). These results indicate that adequate levels of alpha-tocopherol and ascorbate may protect the plasma from oxidative damage elicited by smoking-mediated reactive oxygen species (ROS) and free radicals in young smokers. However, the antioxidant activities of alpha-tocopherol and ascorbate may be overwhelmed by the long-standing oxidative stress elicited by cigarette smoking in elderly subjects.