Vitiligo is a common pigmentary disorder of the skin with selective destruction of melanocytes. The pathogenetic mechanisms in vitiligo have not been completely clarified. The aim of our investigation was to evaluate the oxidative stress in the pathogenesis of generalized vitiligo. Twenty-seven patients with generalized vitiligo and 24 phototype-, age-, and sex-matched healthy controls were included in this study. We analysed serum levels of malondialdehyde (MDA), nitric oxide (NO), and serum activities of superoxide dismutase (SOD) and xanthine oxidase (XO) in the patients with vitiligo and in the controls. We found significantly higher levels of MDA and XO activity (P < 0.001 and P < 0.05, respectively), and a significantly lower level of serum SOD activity (P < 0.05) in patients with vitiligo compared with the controls. However, the increase in the level of serum NO was insignificant (P > 0.05). These results suggest that lipid peroxidation of cellular membrane of melanocytes by free radicals may have a significant role in the pathogenesis of generalized vitiligo.