Two monoclonal IgG1 antibodies (MAbs) were raised against human brain hyaluronectin (HN) and used to characterize tumor HN. They were screened using an enzyme immunological technique (ELISA) combined with the HN property of specific binding to hyaluronic acid. They were shown to detect two different epitopes (HN1 and HN2) in human normal brain as well as in most tumors. Both HN1 and HN2 epitopes were found associated with mesenchymal benign or neoplastic proliferations (e.g. connective areas of fibroadenomas, extracellular matrix of fibrosarcomas) and with reactive connective tissue (e.g. stroma reaction of carcinomas, ground substance of gliomas). The results corresponded with those previously obtained with polyclonal rabbit antibodies and confirmed that HN is a constant marker of desmoplasia. Thus anti-HN MAbs recognize an antigen that is associated with tumor development and will be suitable for targeting.