The prairie deer mouse (Peromyscus maniculatus bairdii) was more common than the white-footed mouse (P. leucopus) in museum collections from the 6 Illinois counties of the Chicago region before 1920 but constitutes only 5% of specimens deposited since 1970. Because white-footed mouse prefers woody vegetation and because prairie deer mouse is limited to prairie or large open habitats, the change in proportion is likely driven by a disproportionate loss of prairie among remaining natural habitat and increases in woody vegetation within grasslands. The decline of the prairie vole (Microtus ochrogaster) relative to the meadow vole (M. pennsylvanicus) and the lack of recent specimens of Franklin's ground squirrel (Spermophilus franklinii) corroborate the hypothesis that prairie habitats have declined much more so than wooded habitats in the Chicago region. Based on extinction models using museum records, it is probable that S. franklinii is already locally extirpated. Regression analysis suggests the white-footed mouse will be the only local Peromyscus in 0–140 years.