The elevated frequency of malignancy in several human congenital immune deficiency states, as well as in patients receiving cytotoxic drug therapy, has formed the vanguard for the theories of immune surveillance. Such theories have much merit and a fair amount of circumstantial and experimental evidence to support them. Moreover, they have served as an enormous reservoir of intellectual stimulation in tumor biology. However, there is a growing body of evidence that suggests that immunosuppression alone does not dramatically predispose to malignancy. A highlight of some of these recent experiments has been the use of congenitally athymic (nude) mice. For example, it has been demonstrated that nude mice raised under conventional or pathogen-free conditions have a similar rate of leukemogenesis as normal heterozygote littermate controls. Moreover, nude mice appear as susceptible as their littermates to a variety of chemically induced tumors. Nonetheless, nude mice raised under gnotobiotic conditions have a significantly increased risk for development of leukemia and lymphoma. The explanation for this elevated frequency of leukemogenesis in gnotobiotic nude mice is unclear, but several experimental systems propose that a critical feature of "leukemia prevention" under conventional conditions is due to non-T cell mediated influences. It is proposed herein to serially investigate the mechanism for this increment of leukemia and lymphoma in gnotobiotic nude mice and attempt understanding through study of specific immune pathways.