When young (6-week-old) BALB/c and also young C57BL/6 mice were inoculated into footpads with spleen cells from normal, syngeneic, aged donors, their response to the inoculum resulted in the enlargement of popliteal lymph nodes (PLN). The degree of PLN enlargement increased as the age of donor mice increased up to age one year. Spleen and lymph node cell populations were highly effective in eliciting the PLN enlargement. Thymus cells and bone marrow cells were moderately effective, but erythrocytes were ineffective. Resident peritoneal exudate cells and spleen adherent cells were much more effective than a whole spleen cell population. The syngeneic response seems to be attributable to a host-versus-graft reaction, since the PLN response was not affected by 2000 rad irradiation of inoculum cells and since the nylon wool-passed spleen T cell population was ineffective as the stimulator. The response was significantly reduced 3 weeks after thymectomy of recipients. PLN enlargement was also observed in older (7-month-old) mice which received spleen cells of younger mice. In this case, however, the response is ascribable to a graft-versus-host reaction, since the inoculation of radiosensitive spleen T cells into footpads resulted in the PLN enlargement. On the other hand, such a stimulatory activity was not found in either lymph node cells or thymus cells. These results suggest that the antigenicity of adherent cells changes with age and that the change is discernible by spleen-locating and short-lived T cells of young mice.