Although clinical data support the concept of a graft-versus-leukemia (GVL) effect following allogeneic bone marrow transplantation (BMT), there are few data to support a similar GVL activity following syngeneic BMT in man. To identify cells with a potential antileukemic activity post-BMT, we monitored the immunological reconstitution in a patient with chronic phase chronic myeloid leukemia (CML) who received a syngeneic BMT from his identical twin brother. Peripheral blood mononuclear cells (PBMC) from the donor prior to the transplant and from the recipient posttransplant were cultured with recombinant interleukin-2 to generate lymphokine activated killer (LAK) cells. LAK cells from both sources lysed the cell line target cells K562 and LCL and also recipient and allogeneic CML target cells in a 51Cr release cytotoxicity assay. Donor-derived LAK cells did not kill normal donor marrow. LAK cells had similar effects on granulocyte-macrophage progenitor cells (CFU-GM): LAK cells from both donor pre-BMT and recipient post-BMT inhibited the proliferation of CFU-GM from the patient's CML cells, but again donor LAK cells did not inhibit the colony growth of normal donor marrow. These results suggest that a syngeneic GVL effect is inducible following BMT in man and that this activity may be truly antileukemic and spare normal marrow progenitors.