Factor J (FJ) is a complement inhibitor that is able to regulate in vitro both the classical and alternative human complement pathways. In the search of its biological significance, we have analyzed FJ levels in synovial fluid from patients with different arthropathies, in which IL-6 levels had been previously measured. The pathologies included in this study were: rheumatoid arthritis (RA) (n = 21), crystal deposition diseases (CDD) (n = 6), osteoarthritis (OA) (n = 23), spondyloarthritis (SpA) (n = 3) and other inflammatory arthropathies (OIA) (n = 4). We found a good correlation between IL-6 and FJ levels (r = 0.33, p = 0.0132) in the 57 processed samples. Synovial fluids had high levels of IL-6 (median: 3000 pg/ml). Besides, we found that FJ levels were elevated (241 +/- 429 micrograms/ml) when compared with NHS (5.32 +/- 2.82 micrograms/ml). Considering OA patients as control group for non-inflammatory situation, we found that FJ levels were significantly elevated in inflammatory patients only if RA patients were excluded. Furthermore, there were also significant differences with CDD patients. In addition, we have examined the presence of this inhibitor in synovial fluid by Western blot after running gels at acid pH and electrophoretical transference at the same pH. In these experiments, we evidenced the presence of a cationic protein immunoreactive with polyclonal and monoclonal anti-FJ antibodies. In conclusion, FJ levels are elevated in pathological synovial fluids. FJ could be an acute phase reactant as other molecules present in the synovial fluid, or could be shed from extracellular matrix as a consequence of the high enzymatic activity present in the articular fluid or as a response to the inflammatory stimulus.