Houseflies, fleshflies, and blowflies will be used as test animals in a study of the mechanisms involved in insect resistance to insecticides and the role these mechanisms play in the physiology of insects. Both in vitro and in vivo methods will be used in a study of toxicity and synergism of insecticides, the regulation of the enzymes of detoxication, genetic control of resistance factors, and the physical and chemical characteristics of the enzymes involved. The enzymes to be investigated include DDT-dehydrochlorinase, aldrin and heptaclor epoxidase, p-nitroanisol, o-demethylase, juvenile hormone microsomal esterase, and ecdysone oxidase. The spectral study of cytochrome P-450 will be continued and the spectrophotometric techniques will be used in monitoring our attempts to fractionate P-450 from insect microsomes. If this work is successful, we will begin a comparison of P-450 from resistant and susceptible houseflies and from other diptera. We hope to begin culturing insect cells, from houseflies if possible but from lepidoptera if not, to further our studies on the regulation of the microsomal oxidases and other enzymes and of the effect of these enzymes on the metabolism of insect hormones. We will continue our investigation of the metabolism of juvenile hormone and of ecdysone by the oxidases and esterases of both soluble and particulate fractions of insect tissues.