The tumor-inducing capacities of adenovirus type 2-, adenovirus type 12-, and SV40-transformed LSH hamster embryo cells define a spectrum of four distinct tumorigenic phenotypes: type I, nononcogenic for newborn hamsters but oncogenic for nude mice; type II, oncogenic for newborn hamsters but nononcogenic in syngeneic adults; type III, oncogenic for both newborns and syngeneic adults; and type IV, almost equally oncogenic for syngeneic and allogeneic adult hamsters. Modulation of the cellular immune response of the recipient hamster by immunosuppression or by alloimmunization alters tumor susceptibility, suggesting that dynamic transformed cell-host cellular immune interactions determine the tumorigenic phenotype of a transformed cell line. There is no correlation between the immunogenicities of the transformed cell lines tested and their tumor-inducing capacities. However, a strong correlation exists between the ability of transformed hamster embryo cells expressing phenotype IV to produce tumors in allogeneic CB hamsters and their resistance to cytolysis in vitro by activated macrophages. These data suggest that, in addition to transformation, DNA viruses may convey specific tumorigenic phenotypes to the cells that they infect by inducing cellular traits that determine the inherent susceptibility or resistance of a cell to host cell-mediated immune destruction.