We surveyed the Tapajós–Arapiuns Extractive Reserve in Brazilian Amazonia to investigate hunting of jaguars Panthera onca and pumas Puma concolor. We interviewed 115 people in 45 villages in 2007–2008, and recorded numbers of jaguars and pumas killed and the circumstances associated with each killing. At least 32 jaguars and 22 pumas were killed in the Reserve, most within the last 10 years. However, these are underestimates because people probably did not mention all kills during interviews. The first-order jackknife suggests that the actual mortality for the two species is almost double that reported. Using data from 2006–2007 as a reference we estimated a minimum mortality of 12 jaguars and seven pumas per year in the Reserve. Most animals were killed during chance encounters, a large number of these elicited by domestic dogs. Hunting motivated by livestock predation or perceived risks to human life were rare. Hunters kill large carnivores on sight and thus one alternative to reduce hunting is to take measures that will decrease encounter rates, such as forbidding hunting with dogs. Education and extension programmes are needed to ensure the long-term coexistence of humans and large carnivores in this Reserve.