Endangered southern river otters Lontra provocax (huillin) are confined to southern Chile and three isolated areas of Argentina, the most important being the Nahuel Huapi National Park, where distribution surveys were conducted in 1983, 1995 and 2000. We used these survey data together with a Geographical Information System analysis to elucidate the factors that are important in determining huillin distribution at different ecological scales. There were significant heterogeneities in the distribution of huillin between river basins, between habitats, between lakes relative to dispersal routes and topography, and between sample points within a lake. From these analyses three factors emerge as potentially related to huillin distribution, and further elucidation of these are suggested as priorities for research to underpin the species' conservation. These factors are: a) the distribution of crustacean prey, with absence of huillin from one river basin and from mountainous streams correlated with low densities of crustaceans in these places; b) human habitation, which may explain why huillin dispersed southwards, but not northwards, from the main lake, although underwater visibility may also be relevant; c) the presence of the introduced American mink Mustela vison, because although there was a positive relationship between the occurrence of mink and huillin in Lake Nahuel Huapi, there was a negative relationship in their occurrence between other lakes. We discuss possible explanations for all three factors.