The type II collagen induced arthritis animal model (CIA) provides opportunities to study the nature of autoimmune reactions leading to arthritis and is also a useful model for rheumatoid arthritis (RA). Thus, in similarity with RA, the CIA when induced with autologous type II collagen, shows a chronic and progressive disease course. The susceptibility to both RA and CIA are correlated to the expression of certain MHC class II allotype genes. In both diseases autoantibodies to type II collagen and rheumatoid factors are produced. Immunohistopathology of affected joints show in both diseases a dominance of activated macrophages/fibroblasts with a significant infiltration of activated T cells. We suggest here that both RA and CIA are dependent on a synergy between delayed type hypersensitivity and immune complex mediated inflammatory mechanisms and that CIA could provide a tool for studies of immunospecific reactions leading to arthritis.