Superantigens stimulate powerful T-cell responses that can have marked effects in vivo, sometimes leading to shock or even death. The demonstration that strong T-cell responses to superantigens in vivo can be followed by tolerance, reflecting either clonal elimination or anergy, has provided important insights into how mature T cells can be regulated. Further progress in understanding the factors that control these responses relies heavily on defining the specific interactions between T-cell receptors, superantigens and major histocompatibility complex molecules which lead to T-cell activation as well as on the characterization of the specific signal transduction events and molecules involved in this activation. Significant progress has been made, during the past year, in the first area and these findings are summarized below; though less information is available in the latter area, recent observations relevant to this issue are discussed.