The identification of L925I, but not V419L substitutions in the voltage-gated sodium channel gene in this strain is consistent with a recent survey reported by Zhu et al, who found that 6 out of 7 strains collected from the state of Virginia carry this genotype. However, only 17 of the 110 populations they examined were screened for pyrethroid resistance, and the presence or strength of metabolic resistance in these strains was not addressed. Several recent studies have indicated that different populations of bed bugs often have different mechanisms of resistance. While Yoon et al. determined that the NY-BB strain did not exhibit enhanced metabolic enzyme activity, additional studies by Romero et al. and Bai do suggest that some bed bug populations may have enhanced metabolic activity as one of their resistance mechanisms. Additionally, a 2007 survey of the tropical bed bug, found that resistance to deltamethrin, permethrin, DDT, malathion, and propoxur was mainly the result of metabolic mechanisms, specifically CEs and GSTs. Thus, we can expect that different bed bug populations within the U.S. and throughout the world may differ dramatically in their levels of resistance and resistance mechanisms, emphasizing the need for continuous surveillance. As bed bugs were essentially absent from the U.S. for a number of decades, very little is known about the molecular biology or genetics of these ectoparasites. Using conventional Sanger sequencing of cDNA clones, Francischetti et al recently reported an analysis of genes expressed and secreted into bed bug saliva. More recently, Bai et al described a small 454 dataset from the Harlan bed bug strain. While this group reported a number of P450 and GST sequences, the fragmented nature of their assembly makes their data concerning the number and phylogenic relationship of these sequences difficult to interpret. Our report adds another 2.5 million reads corresponding to both a long-time laboratory strain and a newly-collected field strain, including many high coverage, full-length descriptions of contigs encoding P450 and CE ORFs. These sequences should be of great assistance to future studies of insecticide resistance and, more generally, to studies of bed bug biology. We observed a number of P450, GST and CE genes which were Everolimus mTOR inhibitor up-regulated in Richmond strain bed bugs compared to the pyrethroid-susceptible control strain. Four of the six up-regulated genes were at or among the most highly expressed of their respective classes, consistent with a prominent role in metabolic resistance to pyrethroid insecticides. We note that bed bugs, similar to another household pest, the German cockroach, have a history of being cross-resistant to many different substrates. Therefore, these up-regulated genes may be indicators of past and potential future resistance to organophosphates and carbamates as well as pyrethroids. Of the bed bug genes identified in this study, CYP2, CYP3, CYP4 and CYP6 family members and the class I GSTs have all be shown to mediate detoxification functions in other insects, whereas the detoxification functions of orthologous CE genes are unclear.