Mesenchymal stem cells (MSCs) are multipotent progenitor cells and interest in MSC therapy has been raised by the observation that MSCs are able to modulate immune responses in vitro and in vivo. Here, we show that MSCs are not intrinsically immune privileged and are capable of inducing memory T cell responses following injection in vivo in immunocompetent hosts. After cotransplantation in recipients that have received sublethal irradiation, allogeneic MSCs can still induce an alloresponse that may result in graft rejection, suggesting that the immunogenicity of allogeneic MSCs are not fully prevented by a nonmyeloablative conditioning regimen. It is still unclear whether the immunogenicity of allogeneic MSCs is also preserved following a fully myeloablative conditioning regimen.