The plasminogen activator (PA)/plasminogen activator inhibitor (PAI) system is believed to be involved in connective tissue remodelling in joint disease and both PA and PAI production has been shown in several cell types in the joint. We quantified immunoreactive PA and PAI in synovial fluid (SF) and correlated their levels to levels of cartilage derived proteoglycans, radiologically visible joint involvement and to signs of local inflammation. PAI-2 concentrations were increased, compared to normal plasma levels, in patients with rheumatoid arthritis (RA) and reactive arthritis, but not in patients with osteoarthritis (OA). Thirty percent of the patients with RA, but no patient with OA had increased concentrations of PAI-1. Increased concentrations of urokinase type PA (u-PA) were found in RA but not in OA. Tissue type PA (t-PA) concentrations were low in both disease groups. SF proteoglycan concentrations did not correlate with levels of PA or PAI. Concentrations of PAI-2 correlated significantly with SF leukocyte count and cytidine deaminase (CD) activity and u-PA concentrations correlated with CD activity. Both PAI-2 and u-PA were detected in supernatants from lysed polymorphonuclear cells. This suggests that in addition to release from synovial cells and chondrocytes these components may also be released from polymorphonuclear cells. Our results support a pathophysiological role for the fibrinolytic system in joint disease, possibly more pronounced in inflammatory disorders than in OA.