We sampled sixty bottomland forest patches in the six southwestern-most counties in Illinois to determine the current status of the cotton mouse (Peromyscus gossypinus). Identification of Peromyscus was based on a modified allozyme electrophoretic technique with the diagnostic GPI-1* locus. Allozymes were isolated from toe-clip samples, rather than liver, and run on a cellulose acetate medium. One hybrid Peromyscus gossypinus-leucopus and one small Peromyscus, carrying a cotton mouse allele at the GPI-1* locus, were identified from 384 individuals screened with this genetic marker. We suggest that cotton mice are an ephemeral species in southern Illinois, disperse into the area occasionally or only during extreme environmental changes and breed with available white-footed mice because of small population size and reduced mate choice.