The frequency of autoimmune processes seems to increase with age. We have studied here whether lymphoid cells of aged mice have the potential to express autoreactivity by the use of the in vivo graft-vs-host (GvH) assay. It was found that spleen cells from old (104 weeks) C57BL mice caused significant enlargement of the popliteal lymph node upon injection into the footpads of syngeneic young or old recipients. Histologically this enlargement presented characteristics of a GvH reaction. This effect, which was not abolished by irradiation of the hosts, was totally cancelled by in vitro irradiation or by anti-θ treatment of the donor cells. These results indicate that T cells from aged mice have the potential to manifest autoimmune reactivity.