OBJECTIVES: The aim of the study was to investigate whether alterations in antioxidative enzyme activities are dependent on their cofactor concentrations in tobacco smokers. DESIGN AND METHODS: Plasma selenium, copper, zinc and iron concentrations, and the activities of related erythrocyte antioxidative enzymes copper-zinc superoxide dismutase (Cu-Zn SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were measured in tobacco smokers and compared with those of nonsmokers. Plasma thiocyanate levels were measured as an index of smoking status. RESULTS: While plasma copper concentration and erythrocyte Cu-Zn SOD activity were significantly higher, plasma selenium concentration and erythrocyte GSH-Px activities were significantly lower in tobacco smokers than in nonsmokers. There was no significant difference in plasma iron and zinc concentrations or erythrocyte CAT activity between the two groups. There were significant positive correlations between erythrocyte GSH-Px and plasma selenium levels, between Cu-Zn SOD and copper levels, and between CAT and iron levels, and a negative correlation between plasma thiocyanate and selenium content in tobacco smokers. CONCLUSIONS: These findings suggest that antioxidative enzyme activities change depending on their cofactor concentrations in tobacco smokers.