BACKGROUND Transfusion-dependent bone marrow transplant recipients are routinely transfused with ABO group and RhD-compatible blood components. However, because of the scarcity of RhD-negative blood components, particularly platelets, a policy was developed to transfuse RhD-positive blood components to RhD-negative patients during periods of shortage. METHODS We reviewed the records of 78 RhD-negative patients with hematologic malignancies who received RhD-negative bone marrow and/or peripheral blood stem cells, from June 1995 to August 2000. The patients transfused with RhD-incompatible blood components were screened periodically for evidence of the development of red blood cell (RBC) alloimmunization. RESULTS Three of 78 patients (4%) developed anti-D antibodies after receiving RhD-incompatible platelet transfusions. One of the patients developed evidence of anti-RhD antibodies after receiving 42 units of RhD-positive random donor platelets; the second patient developed such evidence after receiving 6 apheresis platelets and 2 infusions of intravenous immunoglobulin G (positive for anti-RhD). The third patient received 206 RhD-positive random donor platelets and 5 apheresis units. All patients were discharged from the hospital. The overall immunization rate was 4%. Six patients received Rh-incompatible packed RBCs and showed no evidence of neither anti-RhD nor any other anti-RBC antibodies. All 78 patients had received RhD-incompatible platelets throughout their engraftment period. CONCLUSIONS Transfusion of RhD-positive blood components to Rh-negative patients with hematologic cancers, who have received RhD-negative bone marrow and/or peripheral blood stem cells, are at low risk of developing RhD antibodies. These findings allow for a flexible strategy of blood component therapy support for this special patient population during periods of shortage.