Herpesvirus saimiri induces leukemia and/or malignant lymphoma when inoculated into different species of nonhuman primates including marmosets and owl monkeys. No malignant disease, however, has been recognized in the natural host for this virus, the squirrel monkey, although a high percentage of these monkeys are chronically infected with H. saimiri. Furthermore, one species of marmosets, as well as capuchin and some owl monkeys, fail to develop lymphoma following experimental virus infection but developed a chronic infection similar to that noted in the natural host. The availability of susceptible and resistant species made it possible to attempt to delineate those humoral and cellular immune parameters that might correlate both with tumor induction and resistance. The findings from these investigations are reviewed and discussed in relation to vaccine studies in this system as a model for a human herpesvirus vaccine.