Gene transfer has allowed a number of biologic issues in the therapy of hematologic malignancy to be addressed. In autologous bone marrow transplantation, gene marking studies have shown that infused marrow contributes to relapse in acute myeloid leukemia, neuroblastoma, and chronic myeloid leukemia. In addition, double gene marking with distinguishable retroviral vectors has allowed comparison of purging techniques and the ability of different sources of stem cells to repopulate. In allogeneic bone marrow transplantation, genetically modified T cells have proven valuable for the prophylaxis and treatment of viral diseases and may be of use to treat disease relapse. Gene transfer is also being used to modify tumor function, enhance immunogenicity, modify function of adoptively transferred immune system cells, and confer drug resistance to normal hematopoietic stem cells.