Enlargement of the popliteal lymph node (PLN) of 6-week-old mice were elicited by the footpad injection of spleen cells of sex-matched, syngeneic, older mice, but not of 6-week-old mice, in a fashion of host-vs.-graft reaction. Effective stimulating cells in the inoculum seem to be Ia-bearing adherent cells. On the other hand, neither B and T cells nor immunoglobulin-secreting cells were effective for host T cell stimulation. Among nonlymphocytic adherent cells, only those attached to plastic dishes after a 24 h-incubation, enriched in macrophages, showed the stimulatory activity for the young recipients, while cells which had adhered once but detached and became non-adherent during a 24 h-incubation or a crude non-macrophage fraction did not induce the PLN response. Thus, the age-related antigenic change may occur on macrophages but not on dendritic cells. The effective cells should be alive, heat-killed cells being impotent to elicite the response. Such spleen adherent cells of aged mice were found to be also stimulative for age-matched recipients, when they are older than 3 months. Autostimulation by macrophages might be responsible, at least in part, for the age-related change of immune functions.