Functional T lymphocyte subpopulations can be identified in humans by antibodies which detect stable glycoprotein antigens on their surface. Thus, inducer T lymphocytes bear an antigen termed T4 while suppressor T lymphocytes bear an antigen termed T5. Immune homeostasis results from a delicate balance between inducer and suppressor subsets within the T-cell circuit and perturbation in subset dynamics may initiate a wide variety of immunopathological disorders. Here Ellis Reinherz and Stuart Schlossman discuss the present understanding of this circuit, its role in the pathogenesis of a number of diseases and how the human immune response can be manipulated in an orderly way through modulation of selected T-cell subsets.