Aim: Thymosin (T beta 4) may have various biological effects that are relevant to the pathogenesis of rheumatoid arthritis (RA). This study was performed to gain insight into the relevance of T beta 4 in the pathogenesis of inflammatory arthritis. Method: The level of T beta 4 in synovial fluid from patients with osteoarthritis (OA) or RA was measured by enzyme-linked immunosorbent assay. An association between T beta 4 and matrix metalloproteinase (MMP)-1 and MMP-13 (collagenases), MMP-2 and MMP-9 (gelatinases), MMP-7, adiponectin, lactoferrin, vascular endothelial growth factor (VEGF), urokinase-type plasminogen activator (uPA), interleukin (IL)-6, IL-8 and prostaglandin E2 (PGE(2)) in synovial joint fluids from OA and RA patients were investigated. Results: The level of T beta 4 in the synovial joint fluid of patients with OA and RA was (mean +/- SD) 145 +/- 88 and 1359 +/- 1685 ng/mL, respectively. The level of T beta 4 in the synovial joint fluid of RA patients was significantly associated with the levels of MMP-9, MMP-13, VEGF, uPA, IL-6 and IL-8, but not with MMP-1, MMP2, MMP-7, adiponectin and lactoferrin. In contrast, the level of T beta 4 in the synovial joint fluid of patients with OA was not associated with any of these molecules. Conclusions: The results suggest that T beta 4 may play an important role in bone degradation and inflammation in RA but not OA, although nothing is known about the molecular mechanisms mediating T beta 4 in arthritic joints. The role of T beta 4 in arthritis should be studied to understand its relevance to the pathogenic processes in arthritis.