Simple SummaryHouse flies have been global pests of humans and animals since antiquity, and are notoriously difficult to control. Flies in nature are sometimes infected with salivary gland hypertrophy virus (MdSGHV), which prevents them from mating or laying eggs. A better understanding of how the virus works could be helpful for through use as a fly management tool. In this study, we found that infected female flies, which normally do not mate, could be induced to mate by treating them with hormones that are involved in normal fly reproduction. The results provide insight into the mechanisms by which the virus tricks the fly into being unresponsive to male suitors.AbstractInfection with salivary gland hypertrophy virus (MdSGHV) ofMusca domesticaprevents female flies from accepting copulation attempts by healthy or virus-infected males. This study focused on supplemental hormonal rescue therapy for mating behavior in virus-infected female house flies. The inhibitory effect of the virus on mating behavior in females injected withMdSGHV was reversed by hormonal therapy in the form of octopamine injections, topical application of methoprene, or both therapies combined along with 20-hydroxyecdysone. Infected females whose mating responsiveness had been restored continued to have other viral pathologies associated with infection such as hypertrophy of the salivary glands and a lack of ovarian development.