The housefly CYP4G2 is also located on chromosome III. Insect CYP4G is remarkable by having Perifosine orthologs distributed across Insecta. The CYP4G enzymes function as oxidative decarbonylases, catalysing the terminal step in insect hydrocarbon production synthesizing alkanes making up a large part of the cuticular hydrocarbons. If spinosad influence expression of xenobiotic genes including P450 genes, we hypothesize that variation of this response is a selectable trait in adaptation to an environment influenced by spinosad, thus having a resistance potential. Additionally, the coordination of P450 gene expression in response to spinosad can elucidate important new insights into the general response to a xenobiotic compound. This paper thus investigates the constitutive and spinosad-induced expression levels of nine resistance associated housefly P450 genes. CYP6A1 assists in the metabolism of organochlorine- and organophosphate-insecticides and is constitutively over-expressed in an organophosphate-resistant strain as well as in neonicotinoid-resistant strains. CYP6A36 is constitutively overexpressed in a permethrin-resistant strain, whereas no difference was found for CYP6A37. CYP6D1 is constitutively over-expressed in pyrethroid-resistant houseflies and in neonicotinoid-resistant strains. CYP6D3 is constitutively over-expressed in pyrethroid-resistant houseflies and previously reported involved in insecticide resistance in the housefly. CYP6G4 is the potential housefly orthologue of Drosophila melanogaster CYP6G1, where overexpression is correlated with DDT and neonicotinoid resistance. The mitochondrial CYP12A1 and CYP12A2 metabolize a variety of insecticides and xenobiotics and are constitutively over-expressed in the diazinon-resistant Rutgers strain. The 791spin strain has a sex-dependent resistance profile with regard to spinosad. Females were resistant, while males were considered within the range of susceptibility. This could indicate that the responsible gene would be highly expressed in females compared to males in this strain due to the sex-specific resistance pattern. This was only the case for one single gene, CYP4G2. Sex determination in 791spin is due to a factor on autosome III, which led to a hypothesis of the spinosad resistance being due to a factor on the corresponding copy of autosome III. CYP4G2 is located on autosome III, and is induced by permethrin in the permethrin-resistant ALHF houseflies. Multiple carbon-oxygen bonds, including aldehydes, are present in spinosad. Spinosad or initial degradation products of spinosad could be substrates for the CYP4G2 enzyme, which is a decarbonylase enzyme catalyzing cleavage of long-chain aldehydes to hydrocarbons with release of CO2. The increased constitutive expression in females compared to males fits with CYP4G2 as a contributor to spinosad resistance in 791spin. Crossover in male houseflies is rare and it could be suggested that the male factor is connected to a certain low–expressed allele of the CYP4G2 gene, located on the same chromosome. Then females might have another version of the allele, which is expressed at a higher level. Then females would have two highly-expressed copies of CYP4G2, while males have one highlyexpressed copy and one low-expressed copy.