For many years immunologists have been intrigued by a series of potent antigens encoded in the murine genome. These antigens, originally termed minor lymphocyte stimulating (Mls) antigens, are capable of inducing extremely strong T cell proliferative responses when presented in the context of MHC class II molecules. Recently, Mls antigens have been shown to stimulate T cells bearing particular T cell receptor Vβelements, leading to the designation of super-antigens. The endogenous expression of these super-antigens in mice results in the clonal elimination of large numbers of T cells in order to maintain self-tolerance. In this review we discuss the recent identification of endogenous super-antigens as retroviral gene products. In addition, we analyze the role of class II MHC molecules in the presentation of endogenous super-antigens to T cells. Finally, we discuss the dramatic effect of retroviral super-antigens on the T cell repertoire.