The staphylococcal enterotoxins stimulate discrete subsets of T cells depending on their expression of particular V genes. Among these, staphylococcal enterotoxin B (SEB) vigorously stimulates V beta 8+ cells. This stimulation results in proliferation of both CD4+V beta 8+ and CD8+ T cells and eventually to anergy and clonal deletion in the former subset. We have examined the possible role of CD8+ T cells in the response of CD4+ cells to SEB, by in vivo CD8+ T-cell-depletion. We found no qualitative difference in the responses of untreated and CD8+ T-cell depleted mice to SEB; however, a small quantitative difference in deletion was observed. Thus it appears that on the whole the response of CD4+V beta 8+ T cells to SEB is independent of CD8+ T-cell effector function, although the latter may play a partial role.