Mating triggers physiological and behavioral changes in females. To understand how females effect these changes, we used microarray, proteomic, and comparative analyses to characterize gene expression in oviducts of mated and unmatedDrosophilafemales. The transition from non-egg laying to egg laying elicits a distinct molecular profile in the oviduct. Immune-related transcripts and proteins involved in muscle and polarized epithelial function increase, whereas cell growth and differentiation-related genes are down-regulated. Our combined results indicate that mating triggers molecular and biochemical changes that mediate progression from a “poised” state to a mature, functional stage.