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We investigated whether thymopentin, a synthetic pentapeptide derivative of thymopoietin, could enhance the protective effect of interleukin-1 alpha when both administered prior to sublethal irradiation in the C57BL/6 mouse. Thymopentin (10 mg/kg/day/7 days) was injected intraperitoneally in groups of C57BL/6 mice. Then, interleukin-1 alpha was administered on day 7. Twenty hr later, all groups were given whole body sublethal irradiation of 750 rad by 60Co elements. In some groups of mice, treatment with thymopentin was continued for 1 week after irradiation. Efficacy of the combination treatment was assessed by evaluation of mortality, as well as by histologic examination of the brain, testis, bone marrow, heart and spleen. The combination of relatively low doses of interleukin-1 alpha (700 U) with thymopentin yielded a survival which was nearly that observed with interleukin-1 alpha (1000 U) given alone (about 100%). The optimal effect was observed in animals treated for 15 days with thymopentin, either in combination or alone. In addition, incidence and severity of histological lesions were also lower in animals with the some treatment schedule. Our results suggest that the combined treatment thymopentin-interleukin-1 alpha prevents radiation damage in the mouse.