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Natural killer (NK) cell activity was investigated in peripheral blood, synovial fluid, and synovial tissue lymphocytes from patients with rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). Unfractionated lymphocytes, T lymphocytes, and non-T lymphocytes from the 3 compartments of JRA patients had reduced activity compared with that of normal peripheral blood lymphocytes (with p values usually between 0.05 and 0.1). Unfractionated synovial tissue lymphocytes of RA patients also showed reduced cytotoxicity (0.05 less than p less than 0.1), whereas peripheral blood lymphocytes exerted normal NK cell activity. The NK activity was exerted by cells both with and without Fc gamma receptors. The highest cytotoxicity was observed in Fc gamma receptor-positive cells, both in peripheral blood and synovial fluid, since more than 70% reduction in NK activity was found after depletion of Fc gamma receptor-positive cells. No evidence of lymphocytotoxic antibodies or other factors with influence on NK cells was observed in the patients' sera.