Peromyscus leucopus (white-footed mice) and Ochrotomys nuttalli (golden mice) were live-trapped in eight experimental plots of lowland and upland deciduous forest during 2001 and 2004. An outbreak of Cuterebra fontinella (botfly) parasitism occurred on both species of small mammals during the 2001 and 2004 trapping seasons, with peaks in mid-July each year. A second peak of parasitism was observed in late October 2004, which differed greatly from 2001 where only one peak occurred. We suggest that a greater three-dimensional home-range size and pattern of behavioral activity exhibited by P. leucopus led to a greater incidence of parasitism (41.7%) compared to the more arboreal O. nuttalli (6.3%–12.5%). The second outbreak of parasitism appeared to have been the result of a late-summer deluge of tropical weather caused by an exceptionally active hurricane season affecting the southeastern United States.