Transforming growth factor-β (TGF-β), a pleiotropic growth factor, is a potent inhibitor of cellular proliferation in cells of epithelial origin. Recently, it has been suggested that a loss of sensitivity to TGF-β through a loss of expression of TGF-β receptors T β R-I and T β R-II--is associated with tumor initiation and progression. Therefore, to investigate the relationship between TGF-β receptors expression and carcinogenesis of bladder TCC, this study examined the expression of T β R-I and T β R-II in 46 bladder TCC patients using immunohistochemistry. Since histopathological grade is a widely accepted marker of prognosis, the results were compared in relation to the three grades of bladder TCC. The results demonstrated that the loss of TGF-β receptors expression is associated with increasing histopathological grades of bladder TCC. Specifically, both T β R-I and T β R-II were readily detected in all 10 normal bladder mucosa specimens. Likewise, all 6 specimens of grade I TCC samples expressed high levels of both TGF-β receptors. However, among grade II TCC samples, T β R-I and T β R-II were detected in 78% and 89%, respectively: among grade III TCC samples, T β R-I and T β R-II were detected in 45% and 41%, respectively. These results suggested that loss of sensitivity to TGF-β may play a role in the progression of TCC from low to high grade disease.