The expression of interleukin 2 (IL-2), induction of its multisubunit receptor and subsequent interplay of this ligand with its receptor are pivotal events in T-cell activation. Our present understanding of the normal IL-2/IL-2R system and of disorders in this network in disease opens the possibility for more specific immune intervention. Thomas Waldmann discusses the clinical application of IL-2, agents that inhibit IL-2 synthesis and action, and how the anti-IL-2 receptor-directed therapy provides a novel perspective for prevention of allograft rejection and for treatment of graft versus host disease, select autoimmune disorders and certain neoplastic diseases.