Injection of bacterial superantigens such as staphylococcal enterotoxin B (SEB) in adult mice results in initial proliferation of SEB-responsive V beta 8+ T cells followed by induction of a state of non-responsiveness frequently referred to as clonal anergy. We show here that SEB-induced anergy involves selective changes in lymphokine production and that it affects CD4+ V beta 8+ and CD8+ V beta 8+ T cells in different fashions. Whereas both CD4+ V beta 8+ and CD8+ V beta 8+ cells from anergic mice exhibit strongly reduced proliferative capacity and interleukin(IL)-2 production upon restimulation with SEB either in vivo or in vitro the CD8+ subset from SEB-injected mice produces other lymphokines (such as interferon(IFN)-gamma) at normal or slightly increased levels in response to SEB. Changes in the levels of production of IL-2 and IFN-gamma protein correlated well with mRNA accumulation both in vivo and in vitro. Collectively these data suggest that superantigen-induced anergy involves selective changes in signal transduction and/or gene regulation in T lymphocytes.