Spontaneous radiation-induced or radiation leukemia virus (RadLV)-induced leukemias were treated in vivo in an early-to-advanced lymphomatous state by using 1,3-bis(2-chloroethyl)-1-nitrosouea (BCNU). BCNU was given at various times after the tumor induction procedure. Treatment was based upon the findings that the RadLV-derived transplant lymphosarcoma (LSA) tumor was cured with a frequency of greater than 90% and a tumor-resistant state was produced by tumor cure. Death from RadLV lymphomas which had been initiated in newborn C57BL mice by ip injection of RadLV was scored in untreated or BCNU-treated mice. At 150 days after initiation, control mice had developed extensive thymic lymphomas, whereas BCNU-treated mice had developed less extensive tumors, had a reduced incidence by approximately 50% and had an increased survival time. Similar findings were noted for the radiation (190 rad of cobalt-60 gamma rays weekly X 4)-induced thymic lymphoma-bearing C57BL mice. Injection of 10(6) living LSA cells before BCNU treatment greatly decreased the tumor load for all groups treated but also shortened the mean survival time. Challenge of long-term survivors with small numbers of viable LSA tumor cells did not identify any host resistance of the survivors to the transplant LSA tumor and indicated that the induction procedure, whether RadLV or radiation, was strongly immunosuppressive.