Mice that are unresponsive to lipopolysaccharide (LPS) (strain C3H/HeJ) can be rendered LPS-sensitive by the adoptive transfer of bone marrow cells from LPS-sensitive mice (strain C3H/HeN). This model of adoptive transfer was used to evaluate the contribution of lymphoreticular cells to five effects of endotoxin on the host: immunogenicity, adjuvanticity, lethality, induction of interferon, and induction of colony-stimulating factor. C3H/HeJ mice became sensitive to each of these effects after adoptive transfer of bone marrow cells from C3H/HeN mice. The efficacy of transfer was directly proportional to the dose of X-irradiation and inversely proportional to the number of surviving host stem cells. The most effective dose of radiation was 850 rad, and C3H/HeN → C3H/HeJ(x) chimeras prepared at this dose were as sensitive to LPS for each parameter tested as were the C3H/HeN donors except for a threefold greater resistance to lethality than LPS-responsive C3H/HeN mice. C3H/HeN mice could also be rendered unresponsive to LPS by the adoptive transfer of C3H/HeJ bone marrow cells. C3H/HeN chimeras were resistant to all the effects of LPS studied except for the induction of colony-stimulating factor. These results demonstrate that lymphocytes and/or macrophages play a primary role in mediating a number of diverse and seemingly unrelated host responses to endotoxin.