The changes in the T cell repertoire of aging BALB/c mice include an increase of V beta 8 + T cells, most of which have a relatively low density of T cell receptors (TCR). We investigated the response of V beta 8 + T cells to staphylococcal enterotoxin B (SEB), a superantigen from a common bacterium, the anamnestic response to which is thought usually to be part of the defense against infection. The injection of an amount of SEB optimum for V beta 8 + T cell proliferation in young mice induced little or no proliferative response in aged mice, and within one or two days they died in shock with apoptotic cells in the spleen, a sign of T cell-shock caused by SEB. Flowcytometry analysis (FCA) 15 h after SEB injection, when cell division had not yet started, revealed the loss of 90% of V beta 8 + T cells in the blood and of 50% in the spleen in mice of all ages tested. However, conspicuous in the remaining V beta 8 + T cells in the spleens of the young mice but not in those of the aged mice, was an increased cellular complexity, as shown by the fact that light was strongly side scattered in FCA, indicating intracellular re-organization. The remaining T cells in the young could include progenitors for the expanding population of V beta 8 + T cells. As seen in lethal shock, V beta 8 + T cells in the aged are not unresponsive to SEB in vitro. They responded to the antigen by increasing the amount of TCR up to the level of that in young mice, but without proliferation. The proliferation arrest of V beta 8 + T cells of aged mice was found to be an intrinsic defect in in vitro cell mixture experiments, in which they were cocultured with young spleen cells which provided a complete immune microenvironment. It was simultaneously found in vitro that most of the V beta 8 + T cells from aged mice disappeared after antigen stimulation and that their disappearance was prevented by the presence of spleen cells from young mice, although they still did not proliferate. Taken all together the findings suggest that V beta 8+ T cells in the aged are at the end state of maturation and terminate by apoptotic death, causing T-cell shock in response to SEB.