Rodents make foraging decisions by balancing demands to acquire energy and mates with the need to avoid predators. To identify variations in the risk of predation, nocturnal rodents may use moonlight as a cue of risk. Moonlight avoidance behaviors have been observed in many nocturnal rodent species and are widely generalized to small mammals. However, most prior studies have been limited to 1 species or 1 study site, or occurred in modified habitats. We evaluated desert rodent activity patterns in natural habitats from 1999 to 2006 at 62 study sites across the Great Basin Desert of western North America. Rodent activity was examined by livetrapping in open habitats, using the presence of the sand-obligate kangaroo mouse (Microdipodops) as a habitat indicator. Activity patterns were assessed on 69 nights with clear skies and compared to corresponding moonlight values (moon phase and brightness) to evaluate the frequency of moonlight avoidance. Analyses of total activity of all species in the rodent assemblage relative to moonlight showed a distinct nonrandom (triangular-shaped) pattern but no significant correlations. However, individual genera of desert rodents responded differently to moonlight. Only kangaroo rats (Dipodomys) displayed significant moonlight avoidance patterns; they were maximally active at significantly different moonlight levels and avoided bright moonlight to a greater extent than co-occurring rodents. Moonlight seemed to limit the activity of kangaroo rats most strongly on bright nights during waxing moon phases and summer seasons, but not significantly during the spring or fall seasons, or during waning moons. Rather than avoiding moonlight, the activity of deer mice (Peromyscus), pocket mice (Perognathus), and kangaroo mice may be governed by changes in competition with kangaroo rats. Differences in the body size, locomotion, and space use of kangaroo rats relative to other rodents may explain why different moonlight responses were detected, especially if these traits alter how rodents perceive risk from bright moonlight. These findings indicate that moonlight avoidance may be a specialized trait of kangaroo rats rather than a general behavior of nocturnal desert rodents in the Great Basin.