Production of antibodies to IgG and to type I and type II collagen (CI and CII) was analyzed by enzyme-linked immunospot assay in patients with rheumatoid arthritis (RA) and patients with other inflammatory or degenerative joint diseases. Anti-CII-secreting cells, generally in high numbers, were found among mononuclear cells eluted from inflamed synovial tissue in 12 of 13 patients with seropositive RA and 9 of 14 patients with seronegative RA or with undetermined serum rheumatoid factor levels. In contrast, no anti-CII-producing B cells were present among synoviocytes from 4 patients with other joint diseases. In none of 7 RA sera did we find significant levels of anti-CII. Synovial B cells secreting antibodies specific for CI were observed less frequently in patients with RA. These results indicate that measurement of serum antibody levels is not adequate to assess actual autoantibody production in rheumatoid joints and that local autoimmune reactions to CII are common in RA, which implies that collagen-reactive T cells are present within the inflamed joints of RA patients. The possible role of a local collagen autoimmunity in RA is discussed, particularly in relation to its putative role in rheumatoid factor production.