OBJECTIVE We studied the incidence, severity, histopathologic features, and status of infection in a spontaneous polyarthritis which occurs in male DBA/1 mice. METHODS Over a 25-week period, the arthritis was evaluated macroscopically in naive mice of different strains. The histopathology was evaluated at different phases of the disease. Virologic and bacteriologic investigations were performed. RESULTS The arthritis occurs in approximately 80% of aging male DBA/1 mice. The disease is chronic and destructive, and the affected joints are characterized by synovial lining proliferation and infiltration of inflammatory cells, mainly mononuclear. The susceptibility appears to be dependent on both sex-linked and non-sex-linked genes, since female DBA/1 mice are not affected and since male BALB/c housed in the same colony are only marginally affected. CONCLUSION This first description of a spontaneous arthritis in aging male DBA/1 mice should provide new opportunities to study general features of a chronic and intermittent arthritis in a well-characterized strain, in which no generalized aberrations of the immune system have been described.