AbstractObjective. To identify the cells that synthesize EDA‐containing fibronectin (FN) and examine the role of EDA+ FN in the pathogenesis of rheumatoid joint lesions.Methods. Localization of EDA+ FN and c‐Fos protein in rheumatoid joints was studied immunohistochemically by utilizing antibodies for EDA+ FN and c‐Fos. Expression of EDA+ FN was studied by immunoelectron microscopy and in situ hybridization. The amount of EDA+ FN was measured by enzymelinked immunosorbent assay.Results. EDA+ FN was specifically localized in the synovial lining layer of synovium with active rheumatoid arthritis (RA) (n = 17), but not in that with osteoarthritis (n = 4) or with inactive fibrous RA (n = 2). EDA+ FN messenger RNA was localized in the synovial lining layer. EDA+ FN was immunoelectron microscopically localized in the synovial lining fibroblast‐like (type B) cells. EDA+ FN was also detected at the cartilage–pannus junction and on the surface of RA cartilage. Double staining showed that EDA+ FN colocalized with c‐Fos protein in the rheumatoid synovial lining layer. Quantification of EDA+ FN showed that it was highly concentrated in rheumatoid synovial fluids.Conclusion. EDA+ FN is synthesized by the synovial lining fibroblast‐like (type B) cells in situ in rheumatoid synovium, and appears to be expressed in association with activated or transformed states of synovium.