Although there is evidence of a strong association between antimelanocyte autoantibodies and vitiligo, the etiology of vitiligo is still unclear. To elucidate the biological significance of antimelanocyte autoantibodies in vitiligo, we measured the percent cytotoxicity of melanocyte mediated by autoantibody and complement in normal controls (n = 31) and in the patients with active, progressive vitiligo (n = 37). Significant differences in percent cytotoxicity of melanocyte were seen between the control and vitiligo groups (P = 0.0001). There were no significant differences in the percent cytotoxicity of melanocyte between the patients (n = 24) with more than 1 year duration and those (n = 13) with less than 1 year duration. The change of percent cytotoxicity between pre- and post-treatment groups (n = 29) with systemic steroid showed significant differences (P = 0.0243). These findings support the hypothesis that a decrease in the antibody-mediated cytotoxicity against melanocytes may play a role in the improvement of vitiliginous lesions after systemic steroid treatment.