We have investigated whether low-dose total-body X irradiation could suppress the development of lymphoma in AKR mice. Male mice were irradiated with 5 cGy three times a week or 15 cGy two times a week from 11 weeks of age for 40 weeks. The incidences of lymphoma were 80.5% in sham-irradiated mice, 67.5% in mice irradiated with 5 cGy three times a week and 48.6% in mice irradiated with 15 cGy twice a week. Incidence of lymphoma was significantly reduced by irradiation with 15 cGy twice a week (P = 0.006). The mean survival time was significantly prolonged from 283 ± 3 days in control mice to 316 ± 10 days in mice irradiated with 15 cGy twice a week (P = 0.008) and to 309 ± 14 days in mice irradiated with 5 cGy three times a week (P = 0.040). Because about 80% of male AKR mice die of lymphoma, it is likely that the prolonged life span observed in the irradiated mice is due to the reduced incidence of lymphoma.