Chronic allograft nephropathy (CAN) includes pathologic changes of interstitial fibrosis, tubular atrophy, and fibrous intimal thickening. Transforming growth factor (TGF)-beta 1 is a fibrogenic cytokine involved in renal allograft fibrosis. Hypoxia-inducible factor (HIF)-1 alpha is induced as an adaptive response to hypoxia triggering the production of fibrogenic cytokines such as TGF-beta 1. Between January 1995 and February 2005, we performed 71 renal allograft biopsies in 61 recipients. Immunohistochemical studies were performed with an immunoperoxidase technique using as the primary antibody either a rabbit anti-human TGF-beta 1 polyclonal or a mouse anti-human HIF-1 alpha monoclonal reagent. The glomerular TGF-beta 1 expression in recipients diagnosed with glomerulonephritis was significantly greater than other pathologic groups (P < .05), and the glomerular TGF-beta 1 expression in the heavy proteinuria group (>= 2.5 g/d) was significantly greater than the low proteinuria group (<1.0 g/d; P < .05). The tubular and interstitial TGF-beta 1 and HIF-1 alpha expressions in CAN were greater than in other groups (P < .05). The tubular TGF-beta 1 expression among the graft loss group was significantly greater than the graft function group (P < .05).