A novel immunosuppressant, deoxyspergualin, given at doses of 2.5 to 20 mg/kg/day on days -3, -2 and -1 before X irradiation protected BALB/c mice from the lethal effects of radiation in a dose-dependent manner. The dose of radiation that killed 50% of the mice within 30 days was 5.63 Gy for mice receiving radiation alone, but was 7.13 Gy in the mice given deoxyspergualin at 20 mg/kg. Prior administration of deoxyspergualin ameliorated leukopenia and thrombocytopenia induced by sublethal irradiation, and significantly increased the number of femoral spleen colony-forming units (CFU-S) that survived irradiation. Deoxyspergualin also reduced the proportion of CFU-S in S phase, as determined by in vitro sensitivity to hydroxyurea. These findings suggest that deoxyspergualin may be effective in the prevention of hematopoietic injury caused by radiotherapy.