The increase in autoantibodies with age of both experimental animals and humans has been thought to reflect a shift in the antibody repertoire from foreign to self antigens. In mice, before immunization, the age-associated increase in antibodies reactive with a prototypic autoantigen, bromelain-treated autologous erythrocytes (BrMRBC), reflected a 3-fold increase in serum IgM and the number of IgM-secreting spleen cells in old compared with young mice. However, the percentage of the IgM-secreting spleen cell repertoire reactive with BrMRBC in old mice was actually approximately 50% that in young mice. In contrast, after immunization with sheep erythrocytes (SRBC), old mice showed a 5-fold increase in the percentage of IgM-secreting cells reactive with BrMRBC while young mice showed no significant increase. The converse is true for the percentage of IgM-secreting spleen cells in old mice specific for SBRC, which is 10% the number generated by young mice. The increased autoantibody response of old mice is not, however, linked to their poor response to the nominal antigen. Thus, immunization with phosphorylcholine (PC) conjugated keyhole limpet hemocyanin, an antigen that induces a comparable anti-PC response in old and young mice, also induced more autoantibody forming cells in old than young mice. The increased autoantibody response of old mice after immunization can be accounted for by both an increased number of Ig-secreting spleen cells as well as an increased percentage of the expressed repertoire of IgM-secreting spleen cells that react with autoantigens.(ABSTRACT TRUNCATED AT 250 WORDS)