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Interleukin-1 (IL-1) enhanced the capacity of allogeneic bone marrow (BM) cells to promote survival of mice given doses of radiation (1,200 to 1,350 cGy) that are significantly higher than those generally used for BM ablation (850 to 950 cGy). Three to five times greater numbers of lethally irradiated (1,200 to 1,350 cGy) C57B1/6 (H-2b) mice given 10(7) T-cell-depleted Balb/c (H-2d) BM cells survived over 6 weeks if also treated with a single intraperitoneal (IP) dose of 10 micrograms IL-1 20 hours before or from 1 to 3 hours after radiation. The spleens of these mice were reconstituted predominantly, but not exclusively, with donor cells (54% to 91%). Histologic examination of the epidermal and gastrointestinal tissues of mice surviving more than 6 weeks did not reveal any evidence of graft-versus-host (GVH) disease; however, since 10% to 43% of the mice died between days 30 and 46, the possibility of a GVH syndrome in these mice cannot be excluded. The spleen cells from irradiated mice given BM transplants and IL-1, which consisted of greater than or equal to 85% donor cells, were able to generate specific T-cell cytotoxic killing of unrelated allogeneic donor cells but were unreactive to target cells bearing either host or donor major histocompatibility complex (MHC) class I antigens. Thus, long-term mixed chimeric survivors were tolerant to recipient and donor alloantigens but exhibited immunologic competence. These results show that IL-1 promotes survival of lethally irradiated mice and that allogeneic hematopoietic cells in such animals develop tolerance to host MHC antigens. Although there are many unanswered questions, these data suggest that IL-1 may prove clinically useful in promoting BM engraftment.