Abstract Syngeneic memory cells can be stimulated to yield a secondary immune response after their transfer into irradiated euthymic recipients as well as into young thymusless nude mice. It is shown that nude mice older than twelve weeks of age are not permissive towards memory cell activation as it is found in non-irradiated euthymic animals. This barrier to isogeneic or congeneic cells seems to be caused by a pool of cyclophosphamide-sensitive cells. Since young nude mice could be rendered as unpermissive as older nude mice by pretreatment with either PNA-agglutinable thymus cells or nylon-wool passed spleen cells, it is suggested that an increased number of precursor T cells in older nude mice might induce this effect. Further experiments with monoclonal antibodies against the Lyt-1, Lyt-2, and L3T4 marker on T cells indicate that T-helper/inducer activity might be required to establish the ≪isogeneic barrier≫ in nude mice.