Immunopathological abnormalities in senescence-accelerated mice (SAM) were studied by comparison of senescence-prone (SAM-P/1) and senescence-resistant (SAM-R/1) mice. Sera from SAM-P/1 mice contained a number of autoantibodies, including natural thymocytotoxic autoantibody (NTA), anti-nuclear antibodies (ANA) and IgG anti-single-stranded and anti-double-stranded (ss and ds) DNA antibodies. Furthermore, an earlier increase in serum IgG2 levels and an earlier appearance of IgG circulating immune-complexes (CIC) associated with low C3 levels, were observed in SAM-P/1 mice. These serological findings were distinctive features in SAM-P/1 mice, which could almost discriminate these mice from SAM-R/1 mice. In addition, age-associated glomerular mesangial and capillary lesions with granular IgG and C3 deposition were frequently observed in SAM-P/1 mice, whereas SAM-R/1 mice even at 10 months of age showed only mild mesangial lesions. These findings suggest that autoimmune abnormalities may contribute to the accelerated senescence in these mice.