Aspergilloses are opportunistic infections in animals and humans caused by several Aspergillus species, including Aspergillus flavus. Although the immune system of Drosophila melanogaster is extensively studied, little is known about the fly's specific responses to infection by A. flavus. We compared gene expression levels during induced infections in D. melanogaster by a virulent A. flavus isolate and a less virulent isolate, as well as from uninfected flies as a control. We found that 1081 of the 14,554 gene regions detected were significantly differentially expressed among treatments. Some of these up- and down- regulated genes were previously shown to be involved in defense responses against pathogens. Some are known to be involved in vitelline membrane formation in flies. Other up- and down-regulated genes are of unknown function. Understanding expression of these genes during the process of infection in flies should improve our knowledge of innate immunity in invertebrates, and by extension, in vertebrates as well.