Rejection of transplanted tissue allografts results from T-cell recognition of histocompatibility antigens expressed by cells of the donor graft. This review focuses on the phenotype, specificity, and function of the T cells mediating rejection responses against skin allografts, and on the immune mechanisms by which host T cells are either activated or rendered non responsive by cellular populations within the graft. We review the cellular basis for rejection responses across limited class-land class-II major histocompatibility differences, as well as the specificity of the rejection response itself.