Sexual isolation is a form of reproductive isolation that prevents gene flow between different taxa. Drosophila arizonae is a cactophilic fruit fly with a wide distribution in the deserts of North America. Its range overlaps with its sister species, Drosophila mojavensis and another closely related species Drosophila navojoa. D. mojavensis has been extensively studied in the light of reproductive isolation and it is described as a species complex with four different populations that present different levels of reproductive isolation. However, far less is known about the reproductive behavior of D. arizonae. While the four populations of D. mojavensis are strict specialists on different cacti plants, D. arizonae is a generalist cactus feeder and can often be encountered in sympatry with one of the other species. For this reason, the scope of this study is to unravel the mechanisms involved in reproductive isolation of Drosophila arizonae. Among other cues fruit flies use chemical and auditory signals to distinguish suitable mates. Here, we investigate whether forced crosses between D. arizonae and the other cactophilic flies result in fertile offspring, and whether the flies use olfactory and/or auditory signals to circumvent hybridization.