Streptococcal pyrogenic exotoxins (SPEs) A, B, and C, like other members of the pyrogenic toxin family, are able to cause toxic shock-like syndromes. One of the major properties of these toxins is the ability to induce T-cell proliferation. Characterization of T cell mitogenicity associated with SPEs A, B, and C was undertaken. SPEs A, B, and C were mitogenic for C57BL10/SnJ and BALB/cWAT T cells, with activities differing in intensity depending on the mouse strain and toxin employed. SPE-induced, T-cell-proliferative activity was dependent on class II major histocompatibility complex molecules expressed on antigen-presenting cells. The abilities of SPEs A, B, and C to preferentially stimulate murine cells with certain T-cell receptor V beta s were investigated by fluorescence-activated cell sorter analysis. SPE A preferentially activated T cells expressing V beta 8 but not V beta 3, 6, or 11, while SPEs B and C preferentially stimulated T cells which did not express any of the tested V beta s.