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Systematic observations of the defensive behavior of wild rodents have greatly informed the experimental study of anxiety and its neural substrates in laboratory animals. However, as the former work has been almost exclusively carried out in rats, few data are available concerning the reactivity of wild mice to standardized tests of anxiety-related behavior. In the present experiments, we employed ethological measures to examine the behavioral responses of a wild-derived population of house mice (Mus musculus) in the elevated plus-maze. In direct comparisons with laboratory Swiss mice, male wild mice exhibited substantially elevated levels of exploratory activities and an overall “preference” for the open arms of the plus-maze. On re-exposure to the plus-maze, male wild mice showed further increases in open arm exploration, while Swiss mice showed a marked shift to the enclosed parts of the plus-maze. Tested …