In Drosophila, components of the ejaculate such as the protein products of the male accessory gland (Acps), are thought to undergo rapid evolution driven by strong selection in the female reproductive tract. Selection on characters of the reproductive tract is expected to lead to post-copulatory prezygotic isolation and ultimately, speciation. The cactophilic sister species D. arizonae and D. mojavensis are recently diverged, but differ markedly in their ecologies (D. arizonae is a generalist and D. mojavensis is a specializes regionally) and population structures. They are thus an ideal system in which to study the early stages of reproductive isolation and how it might vary among populations with different hosts. We sequenced four Acps from a geographically comprehensive sample of D. arizonae and D. mojavensis and applied the McDonald-Kreitman test to each to reveal departures from neutral expectations indicative of positive selection in the context of relatively isolated, ecologically dissimilar host races. We found that departures from neutrality varied among genes but not among populations. In one Acp, selection appears to be localized in one exon of the gene.