In postinflammatory hypopigmentation and in vitiligo, one observes histologic evidence of melanocyte damage, disappearance of melanocytes, and clinical loss of pigmentation. In the case of vitiligo, this loss of pigment is complete. There is considerable evidence that melanocytes are highly susceptible to autocytotoxic damage and perhaps to specific immunologic damage. We directly compared the susceptibility of cultures of melanocytes (M), keratinocytes (K), endothelial cells (EC), and fibroblasts (F) to hydrogen peroxide damage across a Wide range of concentrations (10^‐7‐10^‐2 M) and analyzed the differences by computerized Probit analysis. Cytotoxicity was measured by three dye techniques: acridine orange/ethidium bromide (AO/EB), fluorescein diacetate (FD), and nigrosin (N). All three assays produced similar results. The order of susceptibility to H₂0₂ was M < EC < K < F. The LD₅₀ of melanocyte targets was two orders of magnitude lower than that of fibroblasts. The AO/EB assay was used to study immunologic cytotoxicity of melanocytes in the presence of sera from vitiligo patients plus either complement or cellular effectors of antibody‐dependent cellular cytotoxicity (ADCC). Eleven vitiligo sera and 11 control sera were contrasted in 4‐ and 16‐hr cytotoxicity assays. Vitiligo patients' sera containing antimelanocyte antibodies induced both complement lysis and ADCC of melanocytes. Thus the melanocyte is highly susceptible to peroxide‐induced damage, complement lysis, and ADCC. In addition, antibodies in vitiligo sera appear to be an important trigger of melanocyte damage by complement and ADCC effectors and are likely to be involved in the melanocyte damage observed in vitiligo.