ABO-incompatible kidney transplantations have previously only been performed after several pre-operative sessions of plasmapheresis followed by splenectomy, and with the conventional triple-drug immunosuppressive protocol being reinforced with anti-lymphocyte globulin and B-cell-specific drugs. We have designed a protocol without splenectomy, based on antigen-specific immunoadsorption, rituximab and a conventional triple-drug immunosuppressive protocol. The protocol called for a 1-month pre-transplantation conditioning period, starting with one dosage of rituximab and followed by full-dose tacrolimus, mycophenolate mofetil and prednisolone. Antigen-specific immunoadsorption was performed on pre-transplantation days -6, -5, -2 and -1. After the last session, 0.5 g/kg of intravenous immunoglobulin (IVIG) was administered. Postoperatively, three more apheresis sessions were given every third day. Twenty-one patients have received transplants with this protocol. The ABO-antibodies (Abs) were readily removed by the antigen-specific immunoadsorption and were kept at a low level post-transplantation by further adsorptions. There were no side effects, and all but one patient have normal renal transplant function. We conclude that after one infusion each of rituximab and IVIG, and antigen-specific immunoadsorption, blood-group incompatible renal transplantations can be performed with standard immunosuppression and without splenectomy, and with excellent short- and long-term results.