A study in insecticide metabolism revealed the important role of ALDH in the detoxification of pyrethroid in mosquito. Multiple detoxification enzymes were identified as a target of pyrethroid activitybased probes in rat proteome, including P450s, UDP-glucuronosyltransferases, Flavin-containing monooxygenase and ALDH. Aldehyde dehydrogenases are a family of enzymes that oxidise a broad range of endogenous, xenobiotic and lipid peroxidation products that contain the highly reactive aldehyde to their corresponding carboxylic acid. In mammals, ALDHs are involved in both the detoxification of aldehydes and the biosynthesis of pheromones. However, few studies of ALDHs have been reported in insects. In Drosophila, ALDHs play a vital role in ethanol metabolism by mediating the oxidation of acetaldehyde to acetate, which is involved in ethanol resistance. In this study, transcript levels for three of the Ae. aegypti ALDH genes were quantified. ALDH9948 was significantly overexpressed in the insecticide-resistant PMD-R strain in almost all developmental stages, except adult males, when compared to the susceptible PMD line. In contrast, ALDH14080 was upregulated relative to the PMD strain only in the ABT-418 hydrochloride larval stage. Quantitative PCR results revealed that insecticide selection increased the expression of these ALDHs, although the overexpression was not observed in all life stages. The altered expression of ALDH9948 and ALDH14080 was confirmed at the protein level, indicating that the increase in these proteins is strongly associated with resistance to permethrin. Inconsistencies between the mRNA and protein levels of the same gene may be caused by differences in post-translational regulation between the different developmental stages. Although high levels of ALDH mRNA were found in the larval stage, there was no protein detected by western blot, suggesting that the protein may be expressed at a level below the BMS-207940 detection limit in early stages. However, low-abundance ALDH was detected by 2D-gel electrophoresis from a large sample of larvae used in combination with the sub-proteome approach for the enrichment of low-abundance proteins. The recombinant ALDH isoforms exhibited oxidase activity to catalyse the oxidation of aldehyde moiety of pyrethroids, but subcellular localisation of individual ALDHs was not investigated further in this study.