Radiation exposure to various systems can result in the development of severe toxicity, known as the acute radiation syndrome, with hematopoietic tissues being acutely susceptible to radiation-induced injury. Usually it is the degree of hematopoietic toxicity that determines the feasibility of further tumor control doses of therapy. Therefore the development of agents capable of protecting hematopoietic tissues could have important clinical applications. The cytokine interleukin-1 (IL-1) has been demonstrated to be an effective agent capable of protecting hematopoietic tissues in vivo from the toxicity associated with radiation exposure. We report here the results of studies designed to further investigate the capability of various cytokines (IL-1 and interleukins-2 and -3) to protect bone marrow-derived hematopoietic progenitors [granulocyte-macrophage and megakaryocyte colony-forming units (CFU-GM and CFU-Meg)] from radiation exposure in vitro. Only IL-1 was effective in protecting CFU-GM and CFU-Meg from radiation-induced toxicity in the range of 1-10 U/ml; however, no protection was observed when the radiation dose was greater than 300 rad. The ability of IL-1 to block radiation-induced toxicity was negated in the presence of an antibody to IL-1. These studies provide further information on the effectiveness of IL-1 in protecting in vitro hematopoietic tissues from toxicity associated with radiation exposure.