Suppressor T cells play important roles in the regulation of immune responses and the mediation of dominant immunologic tolerance. Studies of suppressor T-cell function have been hampered until their recent identification as a minor fraction (approximately 10%) of CD4 ( +) T cells that coexpress CD25. CD4(+)CD25(+ ) T cells have been shown to play a critical role in the prevention of organ- specific autoimmunity and allograft rejection. Because tumor antigens are self- antigens, it is not surprising that CD4(+)CD25(+) T cells also inhibit the induction of tumor immunity. The spectrum of activity of CD4(+ ) CD25(+) cells extends to non-self-antigens, including infectious agents. Indeed, T cell-mediated suppression might be responsible for the low level of chronic infection seen with many pathogens. Interestingly, however, this persistent level of infection might be beneficial to the host and needed for maintenance of immunologic memory. Although CD4(+ ) CD25(+) T cells are capable of inhibiting T(H)2 responses, their role in the suppression of allergic responses has not been firmly established. Depending on the desired immune response, enhancement or restraint of suppressor T-cell function might be required. Therefore immunologic or pharmacologic manipulation of regulatory T-cell populations represents an important future approach to immunotherapy of a wide range of immune responses.