With the purpose of studying a possibility of the so-called "two-stage mechanism" in radiation leukemogenesis, a series of studies was conducted to compare the rate of leukemia development, using RF strain mice divided into a set of groups of mice that received one whole body X-irradiation of 150 r, 250 r, 350 r, respectively, and another set of groups similarly irradiated with respective doses and repeatedly painted with 5% croton oil in benzene solution after irradiation. 1. As a result it has been found that in the group receiving 350 r there was no significant difference in the rate of leukemia development between the group receiving the irradiation only and the group that was painted with croton oil solution in addition to the irradiation. 2. In the group that received 250 r, in the group that received croton oil painting immediately after the irradiation or one week after the irradition, there was observed a distinct increase in the rate of leukemia development, while there was no difference between the group that received croton oil painting before the irradiation and the group that received the X-irradiation only. 3. In the groups that received 150 r of the irradiation, leukemia did not develop but it developed only when croton oil was concurrently painted. This finding suggests that leukemia does not develop even when provirus is activated by X-irradiation, if the promoting agent, croton oil is not administered thereafter. 4. In the case when both X-irradiation and croton oil painting were given there could be recngnized leukemias of the so-called thymic type and the non-thymic type in about the same number. 5. In the group given one whoie body irradiation of 250 r and 100 mg of urethane in five separate doses, leukemia developed at a high rate, but in the group given urethane injection alone one of 8 mice developed leukemia. From these results it seems that the "two-stage mechanism" of cancer development as advocated by Berenblum is applicable to the radiation leukemogenesis, and it is thought that X-irradiation acts as an initiator and croton oil as its promotor. In addition, it is presumed that urethane as an initiator has ability to induce leukemia.