We have utilized a severe combined immune-deficient (SCID) mouse adoptive transfer model to explore thein vivoimmunostimulatory effects of bacterial superantigens (SAg). B cell reconstituted SCID recipients were treated with theStaphylococcusaureus-derived toxic shock syndrome toxin (TSSI-1) alone or in conjunction with syngeneic L3T4+TSST-1-reactive Th, cells. Over several months of study, the repetitive administration of TSST-1 resulted in a prompt, transient increase in serum IgG levels. This response required both biologically active TSST-1 and Th, cells. These findings demonstrate that certain bacterial SAgs can promote Th, cell-dependent B cell activation and differentiationin vivo. These studies strengthen the analogy between SAg-mediated and allospecific Th-B cell interactions responsible for the autoimmune sequelae of graft-versus-host disease.