Bacterial superantigens such as staphylococcal enterotoxin B (SEB) cause in vivo a profoud and long-lasting state of unresponsiveness in ligand-reactive T cells. To test whether presentation of SEB by small resting B cells to ligand-reactive T cells is essential for the induction of T cell unresponsiveness, we analyzed the effect of SEB in B cell-deficient mice. We observed T cell deletion and T cell unresponsiveness in both B cell-deficient mice and control mice. We conclude that presentation of SEB by resting B cells is not a prerequisite for the induction of T cell unresponsiveness in vivo.