Old (6 months) overtly autoimmune female NZB X NZW F1 (B/W) mice were markedly hyporesponsive to sheep erythrocytes (SRBC). The response to SRBC was restored by a) simultaneously injecting lipopolysaccharide (LPS) with SRBC or b) transferring bone marrow and thymocytes with SRBC into lethally x-irradiated (100 R) syngeneic old recipients. The in vitro PFC response of old B/W spleen cells to SRBC was restored by adding in culture a) theta-positive and radioresistant spleen cells from old B/W mice primed with homologous antigen or b) activated T cells from the spleens of lethally x-irradiated (1000 R) old B/W mice injected with old syngeneic thymocytes and SRBC but not horse erythrocytes. Various populations of unprimed lymphoid cells from young (4 to 6 weeks) female B/W mice, which respond normally to SRBC, were not capable of restoring the response of old syngeneic mice in vitro or in vivo. These results suggest the existence of a suppressor of T cell activation and/or B and T cell interaction in old autoimmune B/W mice.