Background: Patients with vitiligo have a markedly increased incidence of antibodies to melanocytes, referred to as vitiligo antibodies. Antibodies to tyrosinase have been reported in some patients with vitiligo, suggesting that vitiligo antibodies may be directed to this enzyme. However, there is considerable controversy as to the frequency with which these antibodies occur, and, hence, about their relevance to the pathogenesis of vitiligo. The frequency with which antityrosinase antibodies occur in vitiligo is critical to evaluate their potential role in the pathogenesis of this disease.Objective: To examine the prevalence of antibodies to tyrosinase in a large group of patients with vitiligo. Design:We examined the incidence of antibodies to enzymatically and immunologically active tyrosinase in patients with and without vitiligo.Setting: Outpatient clinic in referral center. Patients:The study was conducted on serum samples obtained from 54 patients with active (n = 40) and inac-tive (n = 14) uncomplicated vitiligo and from 52 age-and sex-matched individuals without vitiligo.Main Outcome Measure: Presence in the serum of antibodies to enzymatically and/or immunologically active tyrosinase.Results: By immunoblotting, 20 patients (50%) with active vitiligo, 9 of those (64.3%) with inactive vitiligo, and 29 control individuals (55.8%) had antibodies to an antigen that comigrated with tyrosinase. However, by immunoprecipitation DOPA stain and by sandwich enzymelinked immunosorbent assay, none of the vitiligo or control individuals had antibodies to tyrosinase, even though both assays easily detected control antityrosinase antibodies. Conclusion:These results indicate that while antibodies to an antigen(s) that comigrates with tyrosinase are common in patients with or without vitiligo, vitiligo antibodies are not directed to tyrosinase.