Up-regulation of beta6 integrin, which is indispensable to the activation of transforming growth factor-beta1 (TGF-beta1), was investigated in chronic renal allograft dysfunction (CAD). A total of 103 renal biopsy samples (normal, 10; acute rejection, 30; CAD, 63) were immunohistochemically evaluated for expression of TGF-beta1 and beta6 integrin. No TGF-beta1 or -beta6 integrin was detected in normal kidney, but both TGF-beta1 and -beta6 integrin reactivity were observed in the distal tubules in acute rejection, and even greater reactivity was observed in the distal tubules in the CAD samples. Semiquantitative analysis revealed that the reactivity of TGF-beta1 and -beta6 integrin was significantly greater in the CAD kidney than in the normal kidney and the kidney in acute rejection. The results suggest that beta6 integrin as well as TGF-beta1 is up-regulated in CAD and that it may serve as an alternative target for the treatment for CAD.