We have studied the ability of immunized lymphoid cells expanded in IL-2 to mediate the cure of mice with localized and disseminated syngeneic lymphoma. Mice received 500 rad total-body irradiation before injection of tumor into the footpad. Mice were treated 5 d later when a palpable local tumor and disseminated metastases were present. Intravenous injection of in vivo immune lymphocytes cured 93% of all mice, significantly better than any control group (P less than 0.0005). Immune cells, secondarily sensitized to the FBL-3 tumor in vitro, also conferred significant survival benefit (P less than 0.005) when injected intravenously, curing 79% of the animals treated. When these in vitro sensitized cells were expanded in IL-2, 8-10-fold over 7 d, 93% of the animals thus treated were cured, (P less than 0.005). When these cells were grown for multiple generations in IL-2 they retained their ability to cure mice (56% cured, P less than 0.01). This is the first demonstration that intravenous injection of sensitized cells grown in long term culture in IL-2 is capable of curing mice of established local and disseminated syngeneic tumor.