The methods of detection of suppressor cells which are generated during an immune response are reviewed. The requirements and the mechanisms for their induction as well as their relationship to other functionally important cell subpopulations (e.g., helper T cells, cytotoxic T cells) are examined. Their nature and the mechanism of their action are reviewed. The control of the generation of suppressor cells by well-defined subregions of the I region of the MHC is one of the most important recent developments. Suppressor cells have been shown to play an important role in a variety of systems such as allotypic suppression, the poor response of some strains of mice to certain polypeptides, the progress of tumor growth, etc. However, their role in other phenomena such as tolerance to self antigens and thus their involvement in the development of autoimmunity is not yet clear. In the NZB/W murine lupus model loss of suppressor cells has been implicated in the progress of autoimmune disease. Soluble mediators with suppressive activity probably represent the effector molecules derived from suppressor cells. Some of them have now been shown to contain antigens coded by the I-J subregion of the MHC. The mechanism of their action and the target cell varies from system to system and is not yet well understood.