We analyzed the responses of several T cell fractions reactive with superantigenic toxins (SAGTs), staphylococcal enterotoxin A (SEA), or Yersinia pseudotuberculosis-derived mitogen (YPM) in mice implanted with mini-osmotic pumps filled with SEA or YPM. In mice implanted with the SEA pump, SEA-reactive Vbeta3(+)CD4(+) T cells exhibited a high-level protracted expansion for 30 days, and SEA-reactive Vbeta11(+)CD4(+) T cells exhibited a low-level protracted expansion. SEA-reactive CD8(+) counterparts exhibited only a transient expansion. A similar difference in T cell expansion was also observed in YPM-reactive T cell fractions in mice implanted with the YPM pump. Vbeta3(+)CD4(+) and Vbeta11(+)CD4(+) T cells from mice implanted with the SEA pump exhibited cell divisions upon In vitro restimulation with SEA and expressed surface phenotypes as memory T cells. CD4(+) T cells from mice implanted with the SEA pump exhibited high IL-4 production upon in vitro restimulation with SEA, which was due to the enhanced capacity of the SEA-reactive CD4(+) T cells to produce IL-4. The findings in the present study indicate that, in mice implanted with a specific SAGT, the level of expansion of the SAGT-reactive CD4(+) T cell fractions varies widely depending on the TCR Vbeta elements expressed and that the reactive CD4(+) T cells acquire a capacity to raise a memory response. CD8(+) T cells are low responders to SAGTs.