An implicit assumption of the mesopredator release hypothesis (MRH) is that competition is occurring between the larger and smaller predator. When significant competition exists, the MRH predicts that larger species should affect population size, through direct predation or the elicitation of avoidance behavior, of smaller predators. However, there have been few manipulations designed to test these predictions, particularly regarding avoidance. To test whether striped skunks (Mephitis mephitis) avoid coyotes (Canis latrans), we intensively monitored 21 radiocollared skunks in a natural area in northeastern Illinois. We identified 2 spatially distinct groups and recorded 1,943 locations from September to November 2003. For each group, testing periods consisted of 4 weeks (2 weeks pretreatment, 1 week treatment, and 1 week posttreatment). We simulated coyote activity during the treatment week by playing taped recordings of coyote howls at 1-h intervals at 5 locations. Additionally, we liberally applied coyote urine to several areas within 20 randomly selected 100 × 100-m grid cells, and used the grid to classify cells as urine-treated, howling-treated, or control. We determined changes in home-range size and location, and intensity of cell use in response to treatment. We found no differences in home-range size related to treatment (P ≥ 0.248). Although weekly differences in home-range drift approached significance when individuals from both tests were pooled (P = 0.071), drift was highly correlated with mean weekly low temperatures (P = 0.004). Use of howling- and urine-treated cells did not vary among weeks (P ≥ 0.307), nor did proportions of locations within howling circles with assumed effective broadcast radii of 50–200 m (P ≥ 0.851). Examination of our data did not support the prediction that skunks avoid areas of coyote activity on our study site.