Synovial membrane biopsy specimens from 15 rheumatoid arthritis patients were examined using routine histologic stains and monoclonal antibodies directed against cell surface antigens. Three patterns of lymphoid cell infiltrates were recognized: 1) diffuse infiltration of T cells that surrounded clusters of germinal center B cells (3 patients); 2) diffuse T cell infiltration, lacking germinal centers (8 patients); and 3) proliferation of subsynovial fibroblasts, with relatively few lymphoid cells (4 patients). The synovial, subsynovial, and perivascular tissues in each of the patterns exhibited a high frequency of HLA-DR antigen, HLA-DS antigen, transferrin receptor, and/or epidermal growth factor receptor. In contrast, normal or osteoarthritic synovial tissues did not display a marked increase of these antigens or receptors. Cells bearing natural killer antigen were infrequent in each of these patterns. Active synovitis, synovial effusions, anemia, and elevated sedimentation rate were present in rheumatoid arthritis patients with each of the three histologic patterns. Immunohistologic characterization of synovial membrane infiltrates by these monoclonal antibodies provides additional information about pathogenesis of rheumatoid arthritis and may help in predicting responses to different therapeutic modalities.