The T-cell response to pigeon cytochrome c peptide, residues 88-104 (pcytC), in B10.BR mice is mediated largely by cells bearing both V beta 3 and V alpha 11 variable regions of the T-cell antigen receptor. These cells are, therefore, reactive with the superantigen staphylococcal enterotoxin A (SEA). Recent reports have shown that in vivo exposure to superantigen can lead to deletion of superantigen-reactive T cells from the pool of mature T cells in the periphery. Here we show that upon cotreatment of animals with both SEA and pcytC, bulk deletion of the population of SEA-reactive cells is maintained, while the subpopulation of SEA-reactive T cells that also responds to pcytC is not deleted but instead proliferates in response to pcytC. These results are discussed with regard to mechanisms regulating the balance between T-cell tolerance and T-cell activation in vivo