e Emergence of viruses into the human population by transmission from nonhuman primates (NHPs) represents a serious potential threat to human health that is primarily associated with the increased bushmeat trade. Transmission of RNA viruses across primate species appears to be relatively frequent. In contrast, DNA viruses appear to be largely host specific, suggesting low transmission potential. Herein, we use a primate predator-prey system to study the risk of herpesvirus transmission between different primate species in the wild. The system was comprised of western chimpanzees (Pan troglodytes verus) and their primary (western red colobus, Piliocolobus badius badius) and secondary (black-and-white colobus, Colobus polykomos) prey monkey species. NHP species were frequently observed to be coinfected with multiple beta-and gammaherpesviruses (including new cytomegalo-and rhadinoviruses). However, despite frequent exposure of chimpanzees to blood, organs, and bones of their herpesvirus-infected monkey prey, there was no evidence for cross-species herpesvirus transmission. These findings suggest that interspecies transmission of NHP beta-and gammaherpesviruses is, at most, a rare event in the wild. Z oonotic transmission of animal pathogens into the human population is regarded as the major source of new human infectious disease (1-3). Such zoonoses have profoundly altered the course of human history, as reflected by the impact of the bubonic plague, Spanish flu, and HIV/AIDS on human society (4-6). Zoonoses are frequently transmitted to humans following an initial cross-species transmission into an intermediate animal host. Mechanisms underlying cross-species transmission and adaptation to new host species are far from clear but appear to be influenced by multiple factors, including the level and mode of interaction between animal reservoir/transmission source and humans, the phylogenetic relationship of these species, and the nature of the zoonotic pathogen (2,7,8). Zoonotic/enzootic cross-species transmission appears to be a relatively common characteristic of RNA viruses (8). In contrast, the efficiency of cross-species transmission for DNA viruses is unclear. For the Herpesviridae family, transmission appears to be a relatively rare event. In the few instances where virus transmission has been observed, the lack of onward transmission and the uncharacteristically highly pathogenic presentation of overt disease in the new species (e.g., ovine/caprine herpesvirus infection in free-ranging cervids and herpesvirus B in humans) suggest that herpesviruses poorly adapt to their new host environment (9-11).To date, most studies examining cross-species transmission of herpesviruses have been based on phylogenetic analysis of genomic sequences. These studies reveal well-defined genotypic groupings of alpha-, beta-, and gammaherpesviruses within the respective herpesvirus subfamilies Alphaherpesvirinae, Betaherpesvirinae, and Gammaherpesvirinae (12). This phylogenetic distribution has been interpreted as coevolution (co...