Sera from 73 patients, 24 with rheumatoid arthritis (RA), 10 with Sjögren's syndrome (SS, 4 with and six without RA), 17 with Reiter's syndrome (RS), 10 with systemic lupus erythematosus (SLE), 9 with Yersinia arthritis (YA), and 3 with mixed connective tissue disease (MCTD) were examined by enzyme-immunoassay (EIA) for the presence of C3c-binding IgG, IgM, and IgA activity (C3cBIgG, C3cBIgM, C3cBIgA). This activity probably consists of immunoconglutinins and immunoglobulin aggregates. Significantly elevated C3cBIgG was found in the sera of patients with RA (p less than 0.01), SS, and SLE (p less than 0.02). C3cBIgM was elevated in SS and SLE (p less than 0.02). C3cBIgA was increased in RA (p less than 0.005), in SS and YA (p less than 0.02). Correlations of C3c-binding with erythrocyte sedimentation rate, hemoglobin, C-reactive protein, IgG-binding onto platelets, serum IgG, IgM, and IgA levels, and with rheumatoid factors of IgM and IgA classes were computed. C3cBIgG, C3cBIgM, and C3cBIgA correlated significantly with each other, but usually not with other laboratory variables. The exceptions were positive correlations of C3cBIgM with IgM-rheumatoid factors in RA (p less than 0.05), and with serum IgM levels in the whole series of patients (p less than 0.05). The use of C3c represents a new principle to detect abnormalities in the sera of patients with inflammatory rheumatic diseases. However, the pathogenic significance of elevated C3c-binding remains unknown.