Few areas of immunology have been so controversial as that of suppressor T cells. Studies of T cell clones derived from patients with infectious diseases, including leprosy, and allergies have allowed the delineation of functional human T cell subsets. Both CD4 and CD8 cells can be discriminated into subsets that are differentiated by their functions and patterns of lymphokines. Type 1 CD4 cells reactive with lepromin and PPD produce IFN-gamma and IL-2 predominantly, while Type 2 CD4 clones, specific for tetanus toxoid, produce IL-4 and IL-5. Type 1 CD8 cytotoxic T lymphocytes produce predominantly IFN-gamma and IL-2. T suppressor clones derived from immunologically unresponsive lepromatous leprosy patients are antigen-specific, CD8 cells, HLA-DQ restricted, and produce predominantly IL-4, and were designated Type 2 CD8 cells. Several models for peripheral tolerance based on distinct functional T cell subsets are discussed. Previous models of T cell suppression in the mouse and the reciprocal relationship between humoral and cell-mediated immunity in general are reinterpreted in light of such T cell subset interactions.