Sera and synovial fluids from 88 patients with rheumatoid arthritis were examined for circulating immune complexes by three assays: monoclonal rheumatoid factor radioimmunoassay, Clq binding assay, and Raji cell radioassay. Paired samples were available for 82 patients. Immune complexes were detected with high frequency in the synovial fluid by each assay (75% by the monoclonal rheumatoid factor radioimmunoassay, 95% by the Clq binding assay, and 61% by the Raji cell radioassay). In rheumatoid arthritis sera, immune complexes were detected with high frequency by the Clq binding assay (85%) and the monoclonal rheumatoid factor radioimmunoassay (70%) but infrequently by the Raji cell radioassay (26%). The presence of immune complexes in serum was most frequently accompanied by the presence of complexes in fluid, regardless of the method of detection; moreover, the levels of immune complexes in synovial fluid were generally higher than in paired serum. Further, the levels of immune complexes as measured by the Clq binding assay correlated with certain parameters of clinical activity, while the monoclonal rheumatoid factor radioimmunoassay and Raji cell radioassay correlated with extraarticular features (excluding nodules) of rheumatoid arthritis. Available evidence suggests that immunologic processes initiate and/or sustain the inflammation of rheumatoid arthritis. This concept is based in part on the detection of immune complexes and complement abnormalities in both sera and synovial fluids from patients with this disease (1,2). Although numerous methods have been used for the detection of immune complexes, data comparing various procedures in rheumatoid arthritis are limited. The authors have previously presented (3) comparative data on the detection of immune complexes in sera and synovial fluids of rheumatoid arthritis patients by a radioimmunoassay based on reaction with monoclonal rheumatoid factor and gel diffusion procedures that use monoclonal rheumatoid factor and Clq. Immune complexes were detected at similar high frequencies in rheumatoid synovial fluids by precipitin methods and the radioimmunoassay; in contrast, immune complexes were detected with a much higher frequency in rheumatoid sera by the radioimmunoassay than by the precipitin methods. Levels of immune complexes noted by the radioimmunoassay in the sera were generally lower than those found in the synovial fluids. In addition, preliminary data from this and another laboratory have been obtained on the comparison of certain radioassays in various rheumatic diseases including rheumatoid arthritis (4-6). Different patterns of reactivity were observed for various diseases indicating differences in the biologic properties of the immune complexes detected.The frequency and levels of immune complexes by three radioassays (monoclonal rheumatoid factor radioimmunoassay, C 1 q binding assay, and Raji cell radioassay) in rheumatoid arthritis sera and synovial fluids are examined in the present study. Further, the