Significant serum titers of interleukin 2 (IL 2) can be maintained in mice for 12 h after i.p. injection in a 15% gelatin solution. We have tested the ability of IL 2 administered systemically in this fashion to enhance the therapeutic effect of adoptively transferred specifically sensitized lymphoid cells that were expanded in IL 2. Mice with established local and disseminated FBL-3 lymphoma, induced by intrafootpad injection of 10(7) cells after 500 rad total body irradiation, were treated with a combination of i.v. injected murine splenocytes and either murine supernatants containing IL 2 or pure human IL 2 in gelatin. Splenocytes from immune mice were resensitized to irradiated tumor in vitro and were expanded for 7 days in lectin-free IL 2 supernatants. Treatment with these murine splenocytes administered with murine IL 2 supernatants prolonged mean survival to 33.6 days compared with mean survival times of 16.9 days (p less than 0.001) and 23.4 days (p = 0.007) for mice treated with IL 2 alone or splenocytes alone. Human IL 2, purified to homogeneity from the Jurkat cell line, was also capable of improving the therapeutic efficacy of transferred cells in mice. Mean survival was significantly prolonged to 32.1 days when cells and purified human IL 2 were administered, whereas mean survival times of 18.1 days (p = less than 0.001) and 21.5 (p = less than 0.001) were seen for mice treated with IL 2 alone or expanded immune cells alone. Cure rates in this model were also significantly enhanced with the combined treatment of IL 2 and expanded immune cells. Combined immunotherapy utilizing IL 2 and immune cells was thus significantly better than either component used alone. The systemic administration of IL 2 in conjunction with sensitized expanded lymphoid cells may be a useful approach to the immunotherapy of other murine and human tumors.