Long-tailed weasels (Mustela frenata) have an extensive North American geographic range and tolerate a wide range of life zones, excluding some desert ecosystems. However, little is known of their habitat use in landscapes fragmented by agriculture, despite the fact that long-tailed weasel populations may be declining in these landscapes. During late winter-spring and late summer-autumn 1998–2000, we monitored 11 long-tailed weasels (seven males, four females) via radio telemetry to examine patterns of habitat use in an Indiana landscape fragmented by agriculture. Long-tailed weasels exhibited scale-dependent patterns of habitat selection (i.e., habitat selection within a landscape and selection of habitats within home ranges). Weasels selected forest patches, fencerows, and drainage ditches, whereas agricultural fields were avoided. Forest patches and fencerows provided suitable den sites and refuge cover from other predators and exhibited an abundant and diverse prey community. Drainage ditches provided movement corridors and access to free-standing, drinking water. The resource selection patterns and limited dispersal ability of long-tailed weasels compared to other carnivores are consistent with the notion that long-tailed weasels appear sensitive to agriculturally induced fragmentation of habitat.