Severe combined immune deficiency (SCID) mice obtained from different vendors vary in their capacity to accept human tumor xenografts, and in some instances mice must first be irradiated. It has been reported that SCID mice are particularly sensitive to irradiation which, in addition, can partially restore their immune system so that they are no longer totally immunologically incompetent. For the past several years we have used nonirradiated SCID mice to grow human B-cell lymphomas. When we changed vendors, we found it necessary to irradiate the mice before xenografting. Sublethal irradiation of at least one source of SCID mice before tumor cell inoculation improved tumor take and dissemination, but irradiation changed the response of these mice to chemotherapy and immunotoxins. Thus the irradiated mice did not respond to chemotherapy, but the two immunotoxins used for therapy became more effective in extending survival of the mice. It then appears that irradiation affects the immune system of SCID mice in such a way as to change their response to the therapeutic regimens used here.