Cigarette smoking is associated with an increased incidence of atherosclerotic disease. In this study, we examined the mechanism underlying the growth-modulating effects of cigarette smoke extract (CSE) in confluent vascular smooth muscle cells (VSMCs). The treatment of VSMC by CSE decreased the activities of superoxide dismutase (SOD), catalase and glutathione peroxidase of VSMC in a time-dependent manner. In mitogenesis assays using the confluent cells, CSE was not a direct mitogen for VSMC, but potentiated the stimulatory effect of hydrogen peroxides. The reduction of activities of catalase and glutathione peroxidase was partially prevented by SH-containing compounds. In summary, CSE enhanced the mitogenic effect response of hydrogen peroxides, largely depending on the dysregulation of the activities of SOD, catalase and glutathione peroxidase by CSE.