The enterotoxins produced by Staphylococcus aureus (SE) are prototypes of a group of microbial exoproteins that share a potent mitogenic activity for T lymphocytes of several species. These exoproteins use a very effective novel mechanism of T lymphocyte stimulation. For stimulation of all types of T cells (CD4+, CD8+ as well as gamma delta TCR+) the presence of allogeneic or xenogeneic MHC class II molecules on accessory or target cells is required. This requirement is reflected by a selective binding of the toxins to MHC class II molecules. The toxins stimulate preferentially but not exclusively alpha beta TCR+ T cells carrying certain TCR V beta s. A current model suggests that the toxins are functionally bivalent molecules, crosslinking variable parts of the TCR with MHC class II molecules on the accessory or target cells. Of all T cell mitogens the toxins thus most closely simulate T cell recognition of specific antigen. The differential pattern of reactivity of human and murine T cells with various toxins suggests that the toxins have been adapted to the host's immune system in evolution.