Abstract Since the advent of modern immunology, there have been two major principles in transplantation medicine: tolerance and accommodation. Owing to the shortage of cadaveric kidneys in Japan, since 1989, we have performed ABO-incompatible kidney transplantation to expand the indication for kidney transplantation. Through our experience, we have studied the basic and clinical characteristics of accommodation. During the past half-century, we were taught that ABO-incompatible kidney transplantation would result in hyperacute rejection and graft loss within 24 h after transplantation. However, rejection does not occur and the grafts survived in nearly all recipients of ABO-incompatible kidney transplants. We found that accommodation is the mysterious phenomenon responsible for graft survival despite the presence of ABO antigens on graft endothelial cells and of antibodies to these antigens in the recipient's blood. We initially thought that ABO antigens and HLA antigens could not be changed or modified. However, our experience with ABO-incompatible kidney transplantation shows that these two types of antigens differ. ABO antigens are governed by the ABO gene product ABO glycosyltransferase. ABO antigens cannot express antigenicity in the absence of this enzyme. During accommodation, the recipient's ABO genes suppress ABO genes in the graft, thereby inhibiting production of ABO glycosyltransferase. Antigenicity of graft ABO antigens is thus lost, leading to graft survival. Immunosuppressive therapy has been established on the basis of the theory of accommodation. In Japan, ABO-incompatible kidney transplantation has been performed in > 700 patients. Outcomes are similar to those of ABO-compatible kidney transplantation. Throughout the world including Europe and North America, ABO-incompatible kidney transplantation has been evaluated as safe and effective as ABO-compatible transplantation and is now applied for all types of organ transplantation. Since the discovery of human ABO blood type by Karl Landsteiner in 1901, 100 years were required to break through the wall of ABO blood type, a dream of transplantation medicine. We have delineated the mechanism of accommodation, leading to the establishment of new strategies for immunosuppressive therapy and enabling ABO-incompatible kidney transplantation to be performed throughout the world. We believe that this represents a major advance in transplantation medicine.