Like their AKR/J parent, (CBAT6T6 × AKR/J)F1 mice are carriers of endogenous G-MuLV and present a high incidence of spontaneous lymphoma. However, the F1. hybrids do not present the immunological deficits seen in pre-leukemic AKR/J mice since they respond normally to in vitro PHA stimulation and to in vivo LPS immunization. These observations suggest that there is probably no direct relationship between the presence of MuLV and immunological impairment. Studies have been carried out to ascertain whether the altered immunological reactivity seen in AKR/J mice is related to factors intrinsic to the immunocompetent cells or to environmental inadequacy. Thus, (CBAT6T6 × AKR/J)F1 mice were thymectomized, irradiated, reconstituted with syngeneic bone marrow and simultaneous transplant of CBAT6T6 and AKR/J thymus, and their lymphocyte response to PHA was assayed. In addition, antibody production following LPS immunization was studied by transferring AKR/J splenic cells to irradiated CBAT6T6 or (CBAT6T6 × AKR/J)F1 mice, and vice-versa. The results of these investigations indicate that an intrinsic lymphocyte hyporeactivity is present in AKR/J mice and environmental factors do not modify the reactivity of the transferred immunocompetent cells.