Successful immunotherapy of established B16 melanoma metastases in C57BL/6 mice can be achieved by antibody-targeted interleukin-2 administration. This therapeutic effect is accompanied in approximately 20% of the animals by induction of a population of lymphocytes that migrates to and substantially disrupts the cytoarchitecture of the skin, which results in progressive alopecia. The histologic changes associated with the hair loss, i.e., peri-, and intrafollicular inflammatory infiltrates consisting of both activated CD4+ and CD8+ T cells, as well as expression of major histocompatibility complex class I antigens on subinfundibular follicle epithelium, are similar to those observed in human alopecia areata. Furthermore, the alopecic phenotype can be transmitted horizontally by passive transfer of lymphocytes from treated animals to naïve mice. Since lymphocytes from treated animals either lacking or displaying signs of alopecia are able to transmit these phenotypic changes to a similar percentage of naïve animals, the initiation of alopecia seems to be dependent on the coincidence of at least two different events: the presence of specific lymphocyte populations as well as specific features of the skin disclosing a target for these cells.