Superantigens are microbial agents that have a strong effect on the immune response of the host. Their initial target is the T lymphocyte, but a whole cascade of immunological reactions ensues. It is thought that the microbe engages the immune system of the host to its own advantage, to facilitate persistent infection and/or transmission. In this review, we discuss in detail the structure and function of the superantigen encoded by the murine mammary tumor virus, a B-type retrovirus which is the causative agent of mammary carcinoma. We will also outline what has more recently become known about superantigen activity associated with two human herpesviruses, cytomegalovirus and Epstein-Barr virus. It is likely that we have only uncovered the tip of the iceberg in our discovery of microbial superantigens, and we predict a flood of new information on this topic shortly.