We recently described a spontaneously occurring, inflammatory and erosive joint disease in male DBA/1 mice. A major question is whether specific immune reactions are involved in eliciting this disease. The possibility that collagen autoimmunity might constitute one pathogenic factor was particularly interesting as this spontaneous arthritis appears to be genetically restricted in a way similar to collagen-induced arthritis. In the present study, we demonstrate increased serum antibody levels to collagen II in a fraction of the male DBA/1 mice, but not in age-matched female controls. Administration of antibodies with an anti-idiotypic activity to anti-collagen II antibodies and with an affinity for determinants present on isolated syngeneic IgG Fc but not on intact IgG, was shown to interfere with the development of the spontaneous arthritis in a manner similar to that earlier documented for collagen arthritis. These observations suggest that mechanisms similar to those operating in collagen-induced arthritis may also be found in the spontaneously occurring arthritis in male DBA/1 mice.