Allograft rejection has been attributed predominantly to alloreactive T cells which recognize intact allogeneic MHC on donor antigen presenting cells (APC). Following transplantation, T cells may also recognize donor derived MHC antigens which have been processed and presented as antigenic peptides in the context of self-MHC by recipient APC-so called indirect allorecognition. This article discusses the possible role of indirect T cell recognition in the graft rejection response with particular emphasis on recent experimental data obtained fromin vivotransplant models. Although the relative contribution of indirect allorecognition to the rejection process remains unclear the available evidence suggests that the contribution of self-MHC restricted T cells to graft rejection may have been underestimated.