The quest for methods to protect cells from the damaging effects of ionizing radiation led to the observation that cytokines, endogenously produced hormone-like polypeptides, are radioprotective. Interleukin-1 and tumor necrosis factor-alpha, given before irradiation, can protect mice from doses of radiation that would be fatal to untreated animals. At lower doses of radiation, the hemopoietic growth factors, interleukin-1, interleukin-4, interleukin-6, tumor necrosis factor-alpha, interferon, and leukemia inhibitory factor can promote recovery when administered after irradiation. Exposure to ionizing radiation selectively induces expression of some cytokines. Recent work suggests that certain cytokines may initiate autocrine/paracrine regulated recovery and repair pathways. Thus, the radioprotective and therapeutic effects of supplementary pharmacological doses of cytokines may act by amplifying innate defenses to ionizing radiation.