Patients with vitiligo have circulating antibodies to pigment cells. To characterize this response further and to identify the antigens defined by vitiligo antibodies, sera of 23 patients with vitiligo and 22 patients with unrelated conditions were analyzed by immunoprecipitation and SDS-PAGE analysis of ¹²⁵I-labeled cell antigens on pigment and control cells. Antibodies to pigment cell antigens were present in 18 (78%) of the patients with vitiligo but in only three (14%) of the control patients (p < 0.05). The antibodies were directed to one or more antigens with molecular weight (MW) in kilo-daltons (kD) of approximately 35, 40–45, 75, 90, or 150. The responses were most commonly directed to the 40–45-kD, 75-kD, and 90-kD antigens. Antibodies to these antigens were present in 74%, 57%, and 35% of vitiligo patients versus in 14%, 9%, and 0% of control individuals. The 35-kD and 90-kD antigens were preferentially expressed on human pigment cells, whereas the 40–45-, 75-, and 150-kD antigens were expressed on both pigment and control cells. These antigens were labeled by the lactoperoxidase technique, suggesting that they are cell surface antigens. These results confirm that antibodies to pigment cells are associated with vitiligo. These antibodies are directed to several cell surface antigens, some of which are preferentially expressed on pigment cells.