The ability of unmanipulated, antilymphocyte serum (ALS)-treated, and X-irradiated nude BALB/c female mice (in their 13th backcross generation) to serve as hosts for 10 human lymphoblastoid cell lines as well as for peripheral blood lymphocytes from healthy humans was compared. The 10 lymphoma lines included 7 previously characterized and reported in the literature. Significant differences with respect to both latency period for tumor appearance and success rate for tumor transplantation were detected among the 3 experimental groups. The unmanipulated mice were poor recipients for lymphoma heterotranplants, and tumors were produced in only two instances. In contrast, 6 tumor lines were successfully transplanted in mice inoculated with ALS, and all 10 lines were successfully transplanted in X-irradiated recipients. Although tumors were readily produced in ALS-treated and X-irradiated mice, no gross or histologic evidence of focal or distant metastases was apparent. Human lymphoblastoid cells were recultured, essentially unchanged, from the heterotransplants from 6 of 7 tumors tested. Although the tumor line HT 1460, originally from a human lymphoma, was successfully transplanted in all 3 groups, only mouse cells were recultured. The use of X-irradiation, rather than ALS, to immunosuppress nude mice offers a more standardized method for heterotransplanting human tumor cell lines and permits ready comparisons between laboratories. Furthermore X-radiation permits transplantation and subsequent study of lymphoblastoid tumors that are otherwise difficult to successfully transplant in nude mice.