Much has been written about the influence of exotic or nonindigenous species on natural habitats and communities of organisms, but little is known of the physical or biological conditions that lead to successful invasion of native habitats and communities by exotics. We studied invasivity factors in headwater streams of the Susquehanna River West Branch, which drains portions of the northern Appalachian Plateau. A replicated (two major tributaries) 3 ?? 3 factorial design was used to determine landscape effects of size (stream order) and quality (land use) on abiotic (physical and chemical) and biotic (fish community structure and function) stream attributes. Seven (21%) of thirty-four fish species (brown trout, common carp, mimic shiner, bluegill, smallmouth bass, fantail darter, and banded darter) collected in the eighteen streams sampled were nonindigenous to the basin. Watershed size (stream orders 1, 3, and 5) significantly affected stream geomorphologic and habitat variables (gradient, width, depth, current velocity, diel water temperature, bank overhang, canopy cover, and woody debris density) but not water-quality variables, while land use in watersheds (conservation, mining, and agriculture) significantly affected measured water-quality variables (alkalinity and concentrations of manganese, calcium, chloride, nitrate, and total dissolved solids) but not stream physical or habitat quality. Both watershed size and land use affected fish-community variables such as presence of particular species, species density, species diversity, tolerance diversity, and mean fish size, but in both cases the effect was transparent to native-origin status of fish species. No relationships were found between occurrence of nonindigenous species in watersheds and trophic structure or functional diversity. Therefore, the hypothesis that reduced species diversity increases vulnerability to nonindigenous species was not supported. However, the spatial variation associated with both water-quality and habitat-quality factors was greater in streams with mixed (those with nonindigenous species) than with exclusively native assemblages. These findings suggest that the mechanism for successful invasion by nonindigenous or exotic species is through change in water or habitat quality associated with human or natural disturbances, such as agriculture and mining activities in watersheds. Biotic factors appear to play no or a lesser role in the invasibility of northern Appalachian lotic systems.