Dogs with canine rheumatoid arthritis had significantly elevated levels of antibodies to canine distemper virus. This increase was particularly seen in the synovial fluids, compared with paired sera, and was not found in dogs with infective arthropathies, osteoarthritis or in osteoarthritis secondary to rupture of the cranial cruciate ligament. Analysis of the immune complexes precipitated from synovial fluids showed immunoglobulins in all types of arthropathy. Western blotting analyses showed reactivity with anti-distemper antisera in immune complexes from dogs with rheumatoid arthritis, but not in immune complexes from dogs with other joint diseases. These results suggest that there are increased immune responses to distemper in canine arthritis and that these may be due to the presence of this paramyxovirus in affected joints. The implications for the role of a possible infectious agent in rheumatoid arthritis in the dog are considerable.