We have previously reported that the superantigen staphylococcal enterotoxin B (SEB) was able to suppress an immune response to sheep red blood cells when administered intravenously to mice. While the capacity of the superantigens to stimulate lymphocytes and accessory cell functions has been thoroughly examined, it is clear that these agents may also exhibit potent immunosuppressive activity both in vivo and in vitro. This SEB-induced immunosuppression was determined by our laboratories to be mediated by a population of T suppressor cells. The suppression may be due to the generation of inhibitory lymphokines, including IL-10 or transforming growth factor beta, following superantigen stimulation. Alternatively, the immunomodulatory activity may be due to the activation of antigen-specific and/or genetically restricted suppressor cells by SEB. The mechanism of activity of these suppressor cells has not been fully defined. In this report we wished to determine whether a suppressor factor generated from SEB-activated T cells in vitro may be responsible for the inhibition of antibody or delayed-type hypersensitivity responses in vivo. We observed that both antibody and delayed-type hypersensitivity responses were inhibited following administration of the SEB-induced suppressor factor. The in vivo inhibitory activity of the SEB-induced suppressor factor was found to be genetically restricted at the "I-J" locus. In addition, monoclonal anti-I-J antibodies recognized the suppressor factor in a haplotype-specific fashion. These results show that the suppressive product of SEB-induced T cells possesses the ability to inhibit, in a genetically restricted fashion, both cellular and humoral immune responses.