Synovial fluid samples from 36 patients with rheumatoid arthritis (RA) and 31 patients with other articular diseases (OAD) were examined for the presence of antibodies to denatured or native human type II collagen. Levels of IgG antibodies to denatured or native human type II collagen, rheumatoid factor, immunoglobulins, and total proteins were assessed in paired samples of serum and synovial fluid from 21 patients with RA and from 14 patients with OAD. Solid-phase radioimmunoassay showed that levels of antibodies to denatured collagen in synovial fluid were significantly higher in RA patients than in OAD patients (median 3,270, range 44-16,816 versus median 919, range 119-5,814; P less than 0.001). These antibody levels were higher in synovial fluid than in the serum of RA patients, but not in patients with OAD. Paired serum and synovial fluid samples showed no correlation between the level of antibodies to denatured collagen and levels of either IgG, IgA, IgM, or rheumatoid factor. Synovial fluid antibodies to native collagen were higher in RA patients. Antibodies to collagen may be synthesized preferentially in synovial tissues and, hence, participate in the perpetuation of RA.