RASI-1 is a novel matrix metalloproteinase which we isolated from an expression cDNA library representing the mRNA of an inflamed synovium obtained from a patient with rheumatoid arthritis (RA). To investigate the involvement of RASI-1 in the pathology of RA, we examined synovial specimens from RA patients with antibodies directed against an unique RASI-1-derived peptide. In comparison to interstitial collagenase, gelatinase A and B, and stromelysin 1, the RASI-1 expression in the RA-synovium is located mainly in the tunica media of blood vessel walls and its synovial localization is not as ubiquitous as that of other MMPs. The tissue inhibitor of metalloproteinases (TIMP-1), although also widely expressed in the synovium, exhibits strong colocalization with RASI-1 in blood vessel walls. While RASI-1 is expressed in blood vessels of the inflamed synovium of an RA patient, its expression was not found in control synovial specimens from patients with luxation and arthrosis. However, RASI-1 expression can also be found in non-inflamed blood vessels of uterine ligaments and skin. RASI-1, although its function and substrates are unknown, could be involved in processes such as neovascularization and angiogenesis or lymphocyte extravasation and thus may participate in joint tissue destruction during RA.