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When bone marrow (BM) cells, isolated from normal (C57BL/6 x DBA/2)F1 mice (H-2b/H-2d), were cultured with leukemic cells for 24 hours, a significant tumor growth suppression, without noticeable tumor cell killing, was found. The level of BM cell-mediated cytostasis of both P815 mastocytoma (H-2d) and L1210 lymphoma (H-2d) cells was dependent on BM-to-tumor cell ratio; 100% growth inhibition was obtained at a ratio of 480/1. In addition, BM cells were found to be able to synergize in suppressing P815 cell growth with lymphoid cells. The synergistic suppressive effects on tumor cell proliferation were observed in BM-spleen, BM-thymus and BM-lymphnode cell co-cultures. The analysis of cytostatic activity of the cell culture supernatants showed that the synergistic leukemia growth suppression could be mediated, at least in part, by cell-derived soluble cytostatic molecules. The data presented herein also indicated that culturing BM cells with either crude supernatant (25%) from allogeneic mixed lymphocyte culture (MLC) or recombinant human interleukin(IL)-2 (20 U/ml) for 20 hours led to a 2-fold increase in their cytostatic activity against both P815 and L1210 cells. Taken together, the results suggest that although normal BM cells are ineffective in tumor cell killing, they may play an important role in cell-mediated effector mechanisms responsible for suppressing leukemia development; and that activated T lymphocytes, through producing cytokine(s), may rapidly upregulate leukemia growth inhibitory activity of BM cells.