A weakly immunogenic tumor, sarcoma T241, was implanted sub-cutaneously on one hind foot of syngeneic C57B1/6 recipients. After 3 weeks of tumor growth, feet bearing primary tumors were amputated and 24 h later liposomal immunotherapy was begun. Treatments, which were given twice a week for 2 weeks, consisted of intravenous injections of liposomes containing either medium alone or medium from concanavalin A-stimulated spleen cells containing lymphokines. Two weeks after amputation, mice were killed for evaluation of lung metastases. Thirty-two percent of the animals treated with liposomes containing lymphokines had no metastases, but only 3, 5, and 0% were metastasis-free in the controls receiving either no treatment, liposomes containing medium alone, or lymphokines alone, respectively. The liposome—lymphokine-treated group also showed significantly enhanced survival, compared with the control groups.In vitrostudies showed significant tumoricidal activity of peritoneal macrophages from liposome-lymphokine-treated animals against T241 cells and B16 melanoma cells, compared with macrophages from control groups. These studies confirm and further extend previous observations by Fidler (1) to yet another malignant tumor model, and thus provide a rational basis for exploration of similar therapeutic approaches to those human cancers with predilection for lung and, perhaps, liver metastases.