Although immune reactions to collagen have been described in several diseases, the pathophysiologic consequences of collagen autoimmunity remain obscure. We have recently described an animal model of polyarthritis which can be induced in susceptible rats or mice by immunization with native type II collagen. Arthritis develops in animals which have high levels of both cellular and humoral immunity to collagen. In rats, arthritis can be passively transferred with purified IgG antinative type II collagen antibodies. There is circumstantial evidence that antibodies are also important for the initiation of arthritis in susceptible mice. Circulating immune complexes do not appear to be involved and we believe the arthritis is caused by binding of antibodies to autologous collagen. There are a number of similarities between collagen-induced arthritis and human rheumatoid arthritis (RA). Many histopathologic changes are similar including synovitis which progresses to pannus formation, development of marginal erosions and eventual cartilage destruction. Both diseases are associated with collagen autoimmunity which appears to be genetically linked to the major histocompatibility locus. However, there are also significant differences. In particular, the antibody reactivity usually found in RA is primarily directed against covalent structural determinants on collagen and not against the conformation-dependent determinants on type II collagen critical to the development of collagen-induced arthritis. Immunity to collagen has also been described in other animal models of disease and in other human diseases but its relevance to their pathophysiology is unknown. By further characterizing the specific reactions involved including the nature of the immune response, its specificity and the genetic factors important in the host; insight may be gained into the role of collagen autoimmunity in human disease. While significant progress has been made in all of these areas during the last several years, much remains to be learned before the relevance of collagen autoimmunity to any human disease is established.