Objective: To analyse matrix metalloproteinases (MMPs) and tissue inhibitor-1 of MMPs (TIMP-1) levels in the systemic circulation and synovial fluid (SF) of patients with RA and to compare these levels with inflammatory and collagen degradation markers. Methods: ProMMP-1, -2, -3, -8, -9, TIMP-1, levels of MMP/ α2-macroglobulin complexes, and collagen degradation products were measured by sandwich ELISA, activity assays, and HPLC in paired SF and serum samples from 15 patients with RA and 13 with OA. Results: MMPs were higher in SF of patients with RA than in OA or controls. MMP levels in SF of patients with OA were higher than in controls. In serum, levels of proMMP-3, -8 and -9 were higher in patients with RA than in OA or controls, whereas only proMMP-8 and -9 were higher in serum of patients with OA than in controls. A strong correlation was seen between serum and SF levels of MMP-8 and -9 in RA. Increased levels of MMP/α2-macroglobulin complexes indicated an MMP/TIMP imbalance in serum and SF in RA. SF hydroxyproline correlated significantly with SF levels of proMMP-9 in RA. Conclusions: Systemic MMP-8 and -9 levels represent the situation in the inflamed joint; MMP-9 is likely to be involved in degradation of joint collagen. The hypothesis of MMP/ TIMP imbalance in RA is strengthened. Chemicals / CAS: alpha 2 macroglobulin, 95568-41-5; gelatinase A, 146480-35-5; gelatinase B, 146480-36-6; hydroxyproline, 51-35-4, 6912-67-0; interstitial collagenase, 9001-12-1; stromelysin, 79955-99-0; tissue inhibitor of metalloproteinase 1, 140208-24-8; alpha-Macroglobulins; Collagenases, EC 3.4.24.-; Enzyme Precursors; Hydroxyproline, 51-35-4; Matrix Metalloproteinase 8, EC 3.4.24.34; Matrix Metalloproteinase 9, EC 3.4.24.35; Matrix Metalloproteinases, EC 3.4.24.-; Metalloendopeptidases, EC 3.4.24.-; MMP8 protein, human, EC 3.4.24.-; pro-matrix metalloproteinase 9, EC 3.4.24.-; prostromelysin, EC 3.4.24.-; Tissue Inhibitor of Metalloproteinase-1