The present study was performed to evaluate the synovium in patients with rheumatoid arthritis (RA) treated with anti-tumor necrosis factor alpha agents (anti-TNFalpha). Synovial tissue specimens were obtained during total knee arthroplasty (TKA) from 42 RA patients (12 men, 30 women). Twenty-one RA patients were given anti-TNFalpha agents (infliximab, n = 12; etanercept, n = 9), while the remaining 21 RA patients were given no such agents.The histopathological findings were compared between specimens from these groups using the histological scoring system reported by Rooney, which consists of six items:degree of synovial hyperplasia, fibrosis, number of blood vessels, perivascular lymphocyte infiltration, focal aggregates of lymphocytes, and diffuse infiltrates of lymphocytes.Clinical laboratory data including C-reactive protein(CRP), matrix metalloproteinase-3 (MMP-3), and disease activity scores including a 28-joint count (DAS28), disease duration, methotrexate (MTX) dose, and glucocorticoid dose were also assessed before surgery. There were no significant differences in total score between anti-TNFalpha and no anti-TNFalpha groups. However, significant differences were observed in scores of synoviocyte hyperplasia and perivascular infiltrates of lymphocytes between the groups. These results suggested that these agents have a suppressive effect on cell proliferation in the lining layer and on perivascular lymphocyte infiltration. However, further studies are necessary to elucidate the mechanisms of these effects.