A 21-mer synthetic peptide (KGEKVDLNTKRTKKSQHTSEG), designated TSST-1(58–78), was constructed from the primary structure of the toxic shock syndrome toxin 1 (TSST-l). The peptide reacted with a panel of neutralizing monoclonal antibodies (MAbs)to whole TSST-l in solid-phase immunoassays. TSST-1(S8-78) promoted the in vitro proliferation of human peripheral blood mononuclear cells (PBMC)in a dose-dependent manner. Minimum dose required for stimulation (P ⩽ .05) was 0.75 µM peptide. This mitogenic effect was abrogated by incubation of the peptide with MAbs to whole TSST-1 before addition to PBMC. The ability of TSST-1(58–78) to stimulate the proliferation of highly purified resting human T cells was analyzed. Significant proliferation (P ⩽ .01) wasobservedonly in the presence of increasing populations of monocytes added to the cultures. Adherent human monocytes exposed to TSSf-1(58–78) released tumor necrosis factor. Thus, some of the immunoregulatory properties attributed to TSST-1 are demonstrated by the region of the toxin represented by the peptide TSST-1(58–78).