Human TCR gamma delta positive T cells can proliferate in response to stimulation with staphylococcal enterotoxins (SEs) or mediate lysis of SE pulsed target cells. In the small number of studies reported, the proliferative response of gamma delta T cells was limited to V gamma 9 negative cells and, in vitro, such responses do not require the presence of MHC class II molecules for antigen presentation. Proliferative responses have been found after stimulation with SEA, SEB and TSST. The cytolytic activity of gamma delta T cells can be mediated by two different mechanisms: either gamma delta T cells specifically interact with SEA pulsed target cells--this is most likely TCR mediated recognition--or gamma delta T cells mediate antibody dependent cellular cytotoxicity (ADCC). This latter reactivity depends on Fc-receptor expression by the gamma delta T cell clones and the presence of SE specific antibodies during the assay. So far cytotoxic gamma delta T cell reactivity has only been found against the highly homologous enterotoxins SEA and SEE. Finally, HLA-class II positive gamma delta T cell clones can present SE to other SE reactive T cells but appear to be relatively resistant to T cell mediated lysis. Taken together, TCR gamma delta positive T cells are able to respond to a number of bacterial superantigens and may therefore be involved in local immune responses to such antigens. This may be especially relevant for those gamma delta T cell subpopulations that are preferentially found in the (intestinal) epithelia where exposure to bacterial superantigens is likely to occur.