Objective: To determine the role of CD4(+) and CD8(+) T lymphocytes in the pathogenesis of alopecia areata. Design: Relapse of alopecia areata was induced in autologous human scalp grafts on Prkdc(scid) mice by injection of activated T lymphocytes derived from lesional skin. CD4(+) and CD8(+) T cells were separated by magnetic beads before injection. Setting: University-based dermatology practice Participants: Eleven patients with either alopecia totalis or severe alopecia areata. Main Outcome Measures: Hair regrowth, hair loss, and immunohistochemical findings of scalp explants. Intervention: Transfer of scalp T cells to autologous lesional scalp explants on Prkdc(scid) mice. Results: Injection of unseparated T cells and mixed CD4(+) plus CD8(+) T cells resulted in significant hair loss (P<.01) in 5 of 5 experiments. However, injection of purified CD4(+) or CD8(+) T cells alone did not result in reproducible hair loss. CD4(+) and CD8(+) T cells induced follicular expression of intercellular adhesion molecule 1 (CD54), HLA-DR, and HLA-A, HLA-B, and HLA-C after injection into scalp grafts. Conclusions: CD4(+) and CD8(+) T cells have a role in the pathogenesis of alopecia areata. It is hypothesized that CD8(+) T cells act as the effector cells, with CD4(+) T cell help. It is now necessary to look for HLA-A, HLA-B, and HLA-C associations with alopecia areata. Therapeutic manipulations that interfere with CD8(+) activity should be examined.