Invasion of exotic species may be regulated either by regional factors (dispersal limitation) or by local site characteristics that influence colonization success (invasibility). To address the latter question, we surveyed crustacean zooplankton and abiotic features of 171 lakes in Missouri, Arkansas, and Oklahoma and examined features associated with presence of the exotic cladoceran Daphnia lumholtzi. The data set was also used to examine variation in zooplankton species composition in this region. Canonical Correspondence Analysis revealed that zooplankton distributions were most strongly correlated with lake fertility and conductivity. Logistic regression analyses showed that D. lumholtzi was more likely to invade larger and more fertile lakes and appeared unaffected by native zooplankton species richness or presence of particular species. Thus, the current study suggests that physico-chemical characteristics are better predictors than zooplankton communities for explaining the regional spread of D. lumholtzi. Nevertheless, the underlying causes for these trends are unclear, as landscape features correlated to the same physical features may also influence dispersal processes, and other unknown differences between lakes may also be important for colonization success.