The passenger lymphocyte syndrome (PLS), often associated with immune-mediated hemolytic anemia after solid organ and hematopoietic stem cell transplantation, is the result of concomitant transplantation of donor lymphocytes along with the donor allograft. Antibodies directed against recipient red blood cells (RBCs) are frequently found in ABO-mismatched solid organ transplants; however, passenger lymphocyte-mediated hemolysis due to Rh-incompatible antibodies has only rarely been reported. In this report, we present a case of severe hemolytic anemia related to the PLS in an ABO-matched renal allograft recipient. The recipient's blood type was A Rh(D) positive; and the donor, who had been previously alloimmunized, was A Rh(D) negative. The renal allograft recipient's hemoglobin abruptly decreased on postoperative day 12 in the setting of a newly positive direct antiglobulin test and anti-D antibodies in the plasma. The patient required intermittent RBC transfusions for ongoing hemolysis during the first 6 months post-renal transplant. Of all reported cases of anti-D-mediated PLS, our patient would seem to have been one of the most severe, as indicated by a nadir hemoglobin of 41 g/L and the need for 23 U of transfused RBCs. A hemolytic anemia occurring after organ transplantation should raise the possibility of donor-derived antibodies directed against the recipient RBCs. Passenger lymphocyte syndrome-associated hemolysis is occasionally severe as in our case, but can be effectively treated with compatible RBC transfusions.