From June 1982 to November 1989, 39 ABO-incompatible living kidney transplants were performed in 38 recipients. Pretransplant therapies included platelets donor transfusion (21/39), 2 to 5 plasmapheresis sessions (39/39), cyclosporin A with or without azathioprine (33/39) along with polyclonal Abs (36/39) and splenectomy at the time of transplantation (37/39). The last patient who received 2 ABO-incompatible transplants was previously splenectomized (end-stage renal failure due to a cortical necrosis following a traumatic spleen rupture). Three other patients who did not undergo a splenectomy at the time of transplantation were not included in that series but hyperacutely rejected their transplants during the first postoperative week. The 31 ABO-incompatible living related donor graft recipients are alive. Graft loss occurred from acute and/or hyperacute rejection in 5 cases (none below 15 years of age) and from chronic rejection in 8 cases. By contrast, among the 8 ABO-incompatible living unrelated donor graft recipients, only one renal graft is still functioning 20 years later. Graft survival rates are better in the group of patients < 15 years (100%, 89%, 78%, and 78% at 2, 5, 10, and 15 years respectively) compared with the group > 15 years (77%, 77%, 64%, and 59% respectively; NS). Today, 20 years later, prospective randomized studies testing different steps in the preparation protocol are still lacking. Plasmaphereses were replaced by double filtration plasmapheresis and immunoadsorption. Splenectomy seems to be a prerequisite for successful ABO-incompatible living kidney transplantation but IV Ig globulins and rituximab are currently being successfully used without splenectomy along with the new immunosuppressive drugs. As the procedure remains unchanged, it might be reserved to patients where cadaver graft could not be a valuable alternative, especially for recipients < 15 years of age with a living related ABO-incompatible donor.