Transplantation of adenovirus type 2-transformed cell-induced newborn tumor lines to different aged hamsters revealed that the cell-mediated host defenses reponsible for tumor graft rejection matured early in the second week of life. When light microscopic examinations were performed during the course of tumor development, the primary histopathological difference between progressing tumors removed from newborn or thymectomized weanling hamsters and regressing lesions from normal weanlings was the lack of an early, mononuclear cell infiltrate in neoplasms from newborn and thymectomized hosts. These results suggest that the maturation of cellular immunity determines resistance to tumor transplantation in this system. This conclusion was supported by the in vitro detection of concanavalin A-responsive lymphocytes in spleens from tumor-resistant suckling but not tumor-susceptible neonatal hamsters. Although the incomplete seeding of thymus-dependent lymphocytes to the peripheral lymphoid tissues of newborn hamsters may partially explain the deficient concanavalin A responses of neonatal spleen cells, there appears to be an additional requirement for a radioresistant, adherent accessory cell population. These findings suggest that the development of a cell-mediated immune response is necessary for the rejection of adenovirus type 2-transformed cells and transformed cell-induced tumors and that this response requires the interaction of T-cells and accessory cell populations.