In human-dominated landscapes, conflict with people is the primary threat to big cat health, welfare, and conservation. Abnormal behavior, such as predation of livestock or attacks on humans, leads to retaliatory killings, often using inhumane methods such as snaring, poisoning, spearing, or blunt-force trauma. Predators injured by snares, traps or gunshots suffer lifelong morbidity. Translocation leads to injuries from intraspecific aggression from resident territory holders, while captivity often results in chronic stress, morbidity and premature death. Conventional approaches to ameliorating human-predator conflict have proved inadequate, and conflict incidents are increasing worldwide. This project takes an innovative approach to assess the potential of using natural chemical signals to deter big cats from situations where anthropogenic threats to their health and welfare are likely. Building on successful trials in Botswana, we will conduct field trials of the use of volatile urine compounds to modify the behavior of wild leopards, tigers, and snow leopards in conflict hotspots in Nepal. We will determine whether the airborne release of candidate compounds deters large felids from using routes that they would normally follow (Hypothesis 1) and encounter humans, and use the results to select compounds to be tested for their potential to reduce the frequency of large felid attacks within livestock enclosures (Hypothesis 2). In Botswana, a component of leopard urine, 3-mercapto-3-methyl-1-butanol (3M3MB), has confirmed both hypotheses and it will be tested in Nepal where leopard densities are higher and conflict more frequent. Behavioral responses of tigers and snow leopards to components of their urine have yet to be measured in the wild, and we will test the performance of 3M3MB and nine additional candidate compounds on each species. Components that perform favorably will be developed further to produce affordable deterrents that will provide a cost-effective and environmentally sustainable new tool to promote tolerant coexistence between big cats and people.