Kidney transplantation has been established as a suitable alternative therapy to hemodialysis. Several new immunosuppressive agents contributed to the remarkable improvements in short-term graft survival. However, the rate of graft attrition over the long term has remained constant despite improvements in early success of transplantation during recent years. The half-life of cadaver kidneys, for instance, has consistently remained at 6-7 years throughout the entire transplant experience. Although chronic rejection is the major cause of organ graft loss over the long term, its etiology is not well defined and the pathophysiology of the process is not well understood. Isografts showing similar features of chronic rejection including functional deterioration and morphological changes, demonstrate that antigen-independent factors may also be important in the development of chronic rejection, as well as antigen-dependent factors.