Purpose: The purpose of this study was to correlate expression of CD44v5 in osteoarthritic synovium, cartilage, and synovial fluid with radiographical, histomorphological, and biochemical data.Methods: Cartilage and synovia specimens of 27 patients with osteoarthritis were histomorphologically assessed according to Mankin and Pelletier, respectively. Extended weight-bearing antero-posterior radiographs were evaluated according to Kellgren and Ahlback. Expression of membrane-bound CD44v5 was analyzed by immunohistochemistry and levels of soluble CD44v5 were determined by ELISA.Results: Expression of CD44v5 in cartilage and synovia was detected in 67% and 59% of the patients, respectively. Immunohistochemical findings in cartilage correlated significantly with structural cartilage changes (p < 0.001). whereas no correlation was found between expression in synovia and inflammatory synovial changes. Additionally, no relationship was evident between CD44v5 expression and radiographical data, but expression in cartilage and synovium was significantly correlated with each other 0, < 0.04). Surprisingly, expression of CD44v5 in both cartilage and synovia was negatively correlated with synovial fluid levels of TNFg (p < 0.03 and p < 0.02, respectively), and no association was evident with levels of IL-lP.Conclusions: The data demonstrate expression of CD44v5 in osteoarthritic cartilage and synovia, probably independent of joint inflammation. But more importantly, expression of this receptor variant in cartilage seems to be strongly related to the degree of cartilage destruction.