A variety of evidence has pointed to immunological involvement in the pathogenesis of alopecia areata (AA). The aim of the present study was to determine whether differential expression of HLA-DR and intracellular adhesion molecules-1 (ICAM-1) occurs in hair structures of patients with longstanding AA, following stimulation with interferon-gamma (IFN-gamma). IFN-gamma was injected i.v. to nude mice grafted with transplants obtained from affected areas of seven patients and of normal individuals. All mice were injected with IFN-gamma or phosphate-buffered saline (PBS) alone for 3 consecutive days. Immunohistochemical studies were performed in specimens of grafts in order to detect the change in adhesion molecules, HLA-DR antigen, and Langerhans cells. ICAM-1 and HLA-DR induction was found to be similar in grafts from AA patients and normal skin grafts in the IFN-gamma injected mice. However, more intraepithelial Langerhans cells were observed in the AA patients' grafts treated with IFN-gamma than in those treated with PBS and in normal grafts treated with IFN-gamma. This study suggests an important role of Langerhans cells in this issue.