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Conventional assessment of disease activity in rheumatoid arthritis (RA) relies upon well established clinical and laboratory tests which may not accurately reflect alterations in the inflammatory infiltrates in the diseased synovial membrane (SM). In this study, knee joint needle SM biopsies were stained with a panel of monoclonal antibodies (MoAbs) by an immunoperoxidase method. In disease tissue, synovial lining cell hyperplasia was not accompanied by cell mitoses. Infiltrating cells expressed the leucocyte common antigen (CD45). Many CD3+ T lymphocytes representative of the CD4+ , CD7+ and CD8+ subsets were seen (usually aggregated around blood vessels), interspersed with CD22+ B lymphocytes. CD4+ cells of the suppressor inducer phenotype were either scanty or absent. Macrophages were found within the lymphoid aggregates and sometimes in isolation. HLA class II antigen expression was widespread (HLA DR > DQ > DP) and found upon lymphocytes, macrophages and other accessor cells, and often interstitially. Vascular endothelium occasionally expressed DR but not DQ or DP. Many of the SM CD7+ lymphocytes expressed HLA DR suggesting activation. HLA DR was less frequently expressed on CD8+ cells. In order to determine the effect of anti-rheumatic drugs upon the SM, changes in SM cell populations were followed in four groups of patients with active RA, over a six months period. In the first group, after the initiation of gold or penicillamine, there was a marked reduction in the SM inflammatory cell infiltrate, in particular reductions of CD7+ and CD4+ cells. Expression of HLA DR and the transferrin receptor were reduced. Throughout the study, CD4+ suppressor inducer cells remained few or absent. In the second group who were well established upon either gold, penicillamine, or hydroxychloroquine, similar SM inflammatory infiltrates were seen as for Group I, but there were no changes in the overall cell infiltrate or HLA class II expression at the end of the six months period. The same was true for the third group who were receiving a non-steroidal anti-inflammatory drug only, and for the fourth group who had refractory RA and received intravenous methylprednisolone + /- intravenous cyclophosphamide. Needle synovial biopsy of the knee joint, in conjunction with the immunoperoxidase method and a simple scoring system is a useful means of assessing the effect of gold and penicillamine therapy in RA.