Summary:Disseminated tumors growing progressively in syngeneic hosts can be eradicated by combination therapy with cyclophosphamide and adoptive transfer of specifically immune T cells. Interleukin‐2 (IL‐2), which induces proliferation of T cells specifically activated by antigen, has substantial therapeutic potential as a reagent for increasing the magnitude of tumor‐specific T cell responses. The purpose of the present studies was to determine the effector mechanisms operative in tumor‐bearing hosts by which subpopulations of immune T cells can mediate tumor eradication, and to determine if thein vivoadministration of exogenous IL‐2 can augment these T cell effector functions. Disseminated leukemia was eradicated by adoptive therapy with the immune Lyt 1+2− noncytolytic T cell subpopulation, under experimental conditions in which cytolytic T lymphocytes could not participate. The Lyt 1+2− subset contains helper/amplifier cells that produce endogenous IL‐2 in response to tumor and effector cells that mediate delayed‐type hypersensitivity reactions. The administration of exogenous IL‐2 following transfer of immune T cells containing this noncytolytic subset failed to augment their therapeutic activity, implying that the amount of IL‐2 being produced endogenously did not limit the antitumor response. Adoptive therapy with purified cytolytic Lyt 1−2+ T cells produced a demonstrable but limited antitumor effect. Since this cytolytic subpopulation lacked helper T cells, the limited activity observed presumably reflected a requirement for an IL‐2‐producing cell. Administration of exogenous IL‐2 following cell transfer satisfied this requirement and markedly augmented the efficacy of adoptive therapy with Lyt 1−2+ T cells. Thus, infusions of exogenous IL‐2, which may have little activity in settings in which helper T cell function is intact, may be of significant benefit for augmenting cytotoxic responses in hosts that are relatively deficient in helper T cells.