The precise mechanisms responsible for the induction of immunological aberrations in vitiligo are unknown. Clinical and experimental evidence suggests that a variety of chemicals may have profound effects on the immune system by influencing antibody and cytokine production. Benzene, a ubiquitous chemical, is the parent compound for phenols, catechols, hydroquinone, and monobenzone – chemicals that induce cutaneous hypopigmentation/ depigmentation and immunological aberrations. The benzene ring bound to human serum albumin therefore was chosen as an antigen to assess the presence of specific antibodies against this ring in patients with vitiligo. Seventy vitiligo patients and 70 age-, race-, and sex-matched controls were studied. Benzene antibodies were detected by an ELISA assay that used the benzene ring bound to human serum albumin (HSA) as antigen and HSA as control. The mean antibody titer for patients was 90 ± 26 (p < 0.05). Twenty-four (34%) of the patients had increased binding to benzene HSA and not to HSA alone. Nine (12.8%) had moderately elevated titers of 52 ± 21. The remaining 15 had significantly elevated titers of 128 ± 32. The mean titer for controls was 16 ± 40. Three (4.3%) of 70 controls had significantly higher antibody titers, with a mean of 64 ± 28. Since benzene derivatives are known to induce depigmentation, the presence of antibenzene antibodies in the sera of patients with vitiligo suggests that environmental and industrial exposure to chemicals containing the benzene ring structure may play a role in the induction of immunopathological injury in some patients.