Abstract T-cell-mediated suppression of human immune responses involves a complex interaction between distinct lymphocyte subsets with suppressor-inducer and suppressor-effector functions. Recent studies with subset-specific monoclonal antibodies have defined a characteristic phenotype of suppressor-inducer cells (CD4 + Leu8 + 2H4 + 4B4 −) that can be distinguished from that of helper cells for antibody synthesis (CD4 + Leu8 − 2H4 − 4B4 +). Similarly, suppressor-effector cells (CD8 + CD11 + Tp44 − can typically be defined as a subset separable from cytotoxic T cells (CD8 + CD11 − Tp44 +). Both antigen-specific and nonspecific interactions are important in suppressor T-cell activation and function. Soluble signals required for differentiation of CD8 + suppressor cells include an indomethacin-sensitive monocyte product and interferon gamma. In contrast, proliferation of the CD8 + suppressor cell subset depends on stimulations first by a product of CD4 + Leu8 + cells, T suppressor cell growth factor, and second by interleukin 2. Although the molecular basis of antigen-specific interactions between CD4 + and CD8 + cells in suppressor cell generation has not been defined, it may involve both conventional, presumably MHC-restricted, interactions between antigen and antigen receptors, as well as anti-idiotypic interactions of suppressor-effectors with determinants on suppressor-inducer receptors. Progress in elucidating requirements for activation, growth, and differentiation of suppressor cells should facilitate long-term culture of such cells and lead to clearer understanding of mechanism of suppressor-cell mediated immunoregulation.