Understanding the vector insect's gene expression response to a virus infection may aid design of control measures for arbovirus diseases. Culicoides sonorensis is a vector of several agriculturally important pathogens, such as epizootic haemorrhagic disease virus (EHDV) that causes disease in ruminants. Two approaches, differential display and suppression subtractive hybridization, were used to identify 400+ Culicoides transcripts that were more abundant in midguts 1 day following an oral meal containing EHDV. Of these, quantitative PCR confirmed seven to be more abundant in virus-fed midguts than controls. One such transcript encodes a putative RNA editase, CsRED1, induced by dsRNA. Transcripts encoding putative receptors involved in cell differentiation included CsLAR, a protein tyrosine phosphatase, and CsFZ2, homologous to the wingless receptor in D. melanogaster. Transcripts encoding putative translation machinery components included CseIF3, CseIF5A and CsRPS6. Overall, the cDNA fragments identified in this study increased in the midgut at one day postfeeding; by 2 days postfeeding, increases in transcript levels shifted from the midgut to the remainder of the infected midge.