Spontaneously cytolytic hamster spleen cells and BCG-activated hamster macrophages were used to examine susceptibilities to nonspecific effector cell-induced lysis among 13 DNA virus-transformed hamster cell lines exhibiting four different tumorigenic phenotypes. Hamster cells transformed by adenovirus type 12 (an oncogenic adenovirus serotype) or simian virus 40 (an oncogenic papovavirus) readily induced tumors in immunocompetent syngeneic hamsters and were relatively resistant to spleen-cell-induced lysis compared to cells transformed by adenovirus type 2 (a non-oncogenic adenovirus serotype) which induced tumors only in immunoincompetent hosts. Simian virus 40-transformed cells, which possess the unusual property of efficient tumor induction in allogeneic hosts, were uniquely resistant to lysis by activated macrophages. These differential patterns of susceptibility to cytolysis suggest an association between the level of transformed cell resistance to lysis by nonspecific host effector cells and the oncogenicity of the transforming virus. Furthermore, these data suggest that tumor-cell properties, other than those commonly associated with neoplastic transformation, determine the level of susceptibility or resistance to host effector cell mechanisms.