Radioprotective agents such as interleukin-1 (IL-1) and tumor necrosis factor (TNF-alpha), when given prior to irradiation, protect animals from radiation damage. However, in vivo administration of these cytokines does not allow one to determine whether the protective effects act directly on the hematopoietic system. In the present study, we subjected male bone marrow cells to in vitro treatment with IL-1 prior to irradiation and bone marrow transplantation. We found that male bone marrow cells pretreated with IL-1 prior to irradiation increased the survival of irradiated female recipient mice when compared with nontreated irradiated marrow cells. In addition, irradiated female recipients that received IL-1-pretreated male donor bone marrow cells displayed an increased presence of male donor cells in their bone marrow, spleen, and thymus for up to 3 months posttransplant. Furthermore, serial transplantation studies revealed that male cells could only be detected in tertiary female recipients who received bone marrow from mice transplanted with IL-1-treated cells. These results indicate that IL-1 pretreatment protects both short-term and long-term repopulating stem cells from an irradiation insult and that these cells are capable of reconstituting the myeloid and lymphoid organs of recipient mice.