A retrospective serosurvey of multi-host feline and canine viruses among carnivore species in southern Africa (n=1018) identified widespread pathogen exposure even in remote protected areas. In contrast to mortality experienced in East African predators, canine distemper virus (CDV) infection among African wild dogs (Lycaon pictus) in Botswana was not associated with identifiable change in pup survivorship or disease related mortality of adults. A disease outbreak of unknown aetiology occurred in the same population over 4 weeks in 1996. Outbreak boundaries coincided with ecotones, not the spatial distribution of contiguous packs, highlighting the potential importance of landscape heterogeneities in these processes. Direct management of pathogens in domestic animal reservoirs is complicated by the apparent complexity of pathogen maintenance and transmission in these large systems. Conservation effort should be focused at securing large metapopulations able to compensate for expected episodic generalist pathogen invasion and attention directed to addressing underlying causes of population depression such as habitat loss and wildlife conflict.