Cytokines, hormone-like proteins that are produced by stimulated cells and tissues, serve as intercellular messengers. The production of an expanding number of recombinant cytokines in pharmacological quantities has permitted an assessment of the benefit they may provide in preserving and restoring functions of tissues compromised by irradiation. Included here are studies indicating that the cytokines interleukin 1, tumor necrosis factor, stem cell factor and interleukin 12 protect mice from radiation lethality when given prior to irradiation, and even in untreated mice these cytokines serve in innate defenses against external stimuli. In contrast, transforming growth factor beta, interleukin 6 and interferon, given before irradiation, sensitize the mice to radiation lethality. Myeloprotection against ionizing radiation and chemotherapeutic drugs by interleukin 1 depends on the regimen of treatment and may be related to the temporary patterns of induced cytokines and to the resulting changes in the cycling status of the progenitor cells. Interleukin 12, through induction and interaction with additional cytokines, has contrasting effects on different tissues, i.e., protecting the bone marrow but sensitizing the gut. Insights gained from such studies into the cellular mechanisms of regulation of radiation-induced damage by cytokines are discussed. Whether a "trade-off" of protection of some tissues and sensitization of other tissues applies to cytokine therapy in humans is unknown.