The immune responses of Drosophila melanogaster to bacterial and fungal infections has been extensively studied. Here we expand from these two groups of pathogens and examined the immune response of Drosophila against a viral pathogen, specifically the birnavirus Drosophila X virus (DXV). We initially developed a screening system utilizing the anoxia sensitivity which is induced by DXV infection. This system allowed us to examine the effect of various mutations, in previously identified innate immune pathways as well as other possible antiviral pathways, on resistance to viral infection. Using this initial screening method we identified both the Toll pathway and RNAi pathway as possible antiviral responses in Drosophila. Furthermore, we found that increased susceptibility to viral infection by alteration of either of these pathways was generally associated with increased viral load in infected flies. Additionally, we developed cDNA clones of the entire DXV genome to use as the basis for examination of the effects of RNAi on DXV infection and for the development of a reverse genetics system. Using these clones, we show that DXV is sensitive to RNAi. Although RNAi does not result in clearing of virus infection, it inhibits viral replication. Our results indicate that both the Toll and RNAi pathways are playing roles in Drosophila's immune response to DXV infections.