African wild dogs (Lycaon pictus) always live at low population densities relative to sympatric large carnivores. This suggests that there are basic ecological reasons for the wild dog's endangered status. We examined the effects of intraspecific and interspecific competition, infectious diseases, foraging success, genetics and human activities on wild dogs. We present data from wild dogs in the Selous Game Reserve, and make comparisons with other populations to identify the limiting factors that are broadly important. The high density of wild dogs in Selous (40 adults/1000 km2) is associated with weak competition from lions and spotted hyenas. Across ecosystems, population density is negatively related to the intensity of interference competition with larger carnivores. Predation by lions and hyenas accounted for 13% of known-cause deaths in Selous and 33–50% in other populations. Intraspecific competition caused 69% of known-cause deaths in Selous, through infanticide and fights between packs, although most of the victims were juveniles with low reproductive value. Infectious diseases had little apparent impact in Selous (4% of deaths) or Kruger National Park (5%), but did play a role in the extinction of a small population in Serengeti. Infectious diseases and competition will generally interact because competitors harbor and transmit the diseases that affect wild dogs. Human activities caused 12% of deaths in Selous, even though it is large (43 000 km2) and does not border large human or livestock populations. Humans were the major agent of mortality in some populations. Foraging success varied little across ecosystems and was not apparently limiting. Mitochondrial DNA (mtDNA) genotypes revealed clinal variation between Selous and distant populations (rather than geographically isolated subspecies, as previously suggested). All wild dog populations have a genetically effective size (Ne) less than 500, so gene flow is necessary to maintain genetic diversity within populations.