There are conflicting results regarding the role of autoantibodies in the pathogenesis of vitiligo. To examine their in vivo effect, human skin was transplanted onto nude mice injected with purified IgG obtained from patients with vitiligo and from controls. The effect was evaluated by several techniques. Dihydroxyphenylalanine staining revealed a marked decrease in the number of melanocytes in skin grafted onto mice injected with patients' IgG. Direct immunofluorescence staining demonstrated the presence of human IgG throughout the epidermis in specimens injected with purified IgG from vitiligo patients. No staining was observed when control IgG was injected. Electron microscopy studies demonstrated a marked decrease in melanin pigmentation with only rare melanosomes and melanocytes detected in grafts injected with patients' IgG. Thus all three techniques showed the destructive effect of vitiligo patients' serum on melanocytes. Our study highlights the important role of autoantibodies in the pathogenesis of vitiligo.