Insight into the spatial ecology of predators might help biologists to design wildlife reserves that maximize conservation success. We investigated the spatial ecology of endangered black-footed ferrets Mustela nigripes during the post-breeding seasons (June–October) of 2007 and 2008 on a 452-ha colony of black-tailed prairie dogs Cynomys ludovicianus in South Dakota, USA. Ferrets of both sexes frequently used areas with an abundance of active openings to prairie dog burrows, suggesting a positive response to refuge and prey. Densities of active burrow openings were similar in areas of same-sex overlap and areas of exclusive space use, which might suggest limited defense of resources by ferrets. However, this result could be expected in our study because much of the study colony contained high densities of active burrow openings. Same-sex home ranges overlapped in area, but the intensity of space use overlap was low. For male ferrets with overlapping home ranges, both males tended to spend low amounts of time in areas of overlap. In contrast, for pairs of overlapping female home ranges, one female frequently used areas of overlap while the second apparently avoided them, suggesting a dominance hierarchy of some sort. Core areas were essentially exclusive. Our data are consistent with the hypothesis of intrasexual territoriality by ferrets in habitats of high quality, which would limit the number of ferrets a habitat supports. Where wildlife managers aim to maximize densities of free-ranging ferrets, it might be beneficial to create reserves that 1) provide each ferret with sufficient prey and refuge, 2) reduce social conflict and competition for space, and 3) facilitate dispersal.