Classification schemes of renal allograft rejection are being revised accordingly. Major attempts are underway to understand ‘C4d-positive humoral rejection episodes’ better. At present, many centres use C4d during the work-up of allograft dysfunction. Basel was the first transplant centre in the world which considered C4d to be a very valuable diagnostic tool and incorporated it into the diagnostic decision-making process. The transplant centre in Basel has gained experience with C4d over the last decade. C4d is regarded as an immunohistochemical marker for a humoral mediated allo-response. Stimulated by the pioneering work by Feucht and colleagues from Munich years ago, C4d has led to major changes in our understanding of kidney transplant pathology. This traditional view currently is under scrutiny. Tubulo-interstitial rejection is a prime example. Consequently, nearly all acute rejection episodes have been classified as ‘cell mediated’. Hence, antibody-mediated rejection episodes frequently remained undiagnosed and unclassified. The difficulties with identifying humoral rejection are due mainly to the lack of typical morphological and immunohistochemical changes characterizing different forms of an antibody response. In particular, the proper identification of humoral rejection episodes after the immediate post-transplantation period causes problems. However, all current classification schemes of renal allograft rejection have major shortcomings. They form the backbone for the clinical decision making, outcome studies and multicentre analyses of the efficacy of new immunosuppressive drugs. Over the past decades, morphological criteria of acute and chronic rejection have been defined, and classification schemes of rejection have been introduced, such as the CCTT and the Banff schemes. The gold standard for the diagnosis of rejection and for guiding patient management is the histological evaluation of a renal allograft biopsy. Antibodies, C4d, diagnosis, rejection, therapy Background