Lethally irradiated genetically resistant (C57 x AKR) mice, unlike non-resistant (C3H x AKR) mice, which display genetic resistance to transplantation of parental C57 bone marrow grafts (GR to BMT), also reject transplanted parental AKR lymphoma grafts (GR to lymphoma). Depletion of natural killer (NK) cell activity of resistant (C57 x AKR) mice by anti-asialo GM-1 serum abrogated the resistance, whereas stimulation of NK cell activity of non-resistant (C3H x AKR) mice by polyinosinic: polycytidillic acid (poly I:C) induced the resistance to parental AKR lymphoma grafts. This shows that NK cells contribute to GR of (C57 x AKR) hybrid mice to parental AKR lymphoma grafts. Further, these results indicate that NK cells which confer genetic resistance to bone marrow transplantation (GR to BMT) in lethally irradiated (C57 x AKR) hybrid mice, also mediate GR to lymphoma transplantation in these mice, thereby linking GR to BMT with GR to lymphoma-leukemia.