Although much of the basic immunological work has been done with mice, little is known about anti-IgG autoantibodies in this species. Dresser (1, 2) has reported the occurrence, in CBA mice, of anti-IgG antibody (Ab)(1) detected by a hemolytic-plaque assay after stimulation with endotoxin or immunization against sheep erythrocytes. IgM rheumatoid factor has also been described in various strains of mice with a systemic lupus erythematosus-like disease (3). Recently, we have tried to induce anti-IgG in mice of the 129/Sv strain by inoculating autologous IgG. To our surprise, we found that the sera of all the animals had, before any inoculation, anti-IgG detectable by agglutination of particles coated with autologous IgG. The possibilities to investigate the mechanism of production and the biological role of this kind of Ab prompted us to undertake a study of the nature and specificity of the mouse anti-IgG.