Mixed-function oxidases (MFO'S) are enzymes that allow insects to tolerate poisonous chemicals such as insecticides and certain plant compounds. Some plants protect themselves from insects (and other herbivores) by making chemical compounds that are toxic to the animals which try and feed on them. The MFO enzymes detoxify chemical compounds, usually by changing their chemical structure. The study of mixed-function oxidase enzymes, therefore, will provide information as to how insects become resistant to insecticides and/or toxic plant chemicals. This proposal involves the use of an insect-plant model system. The insects are fruit-flies of the genus Drosophila, and the plants are columnar cacti which grow in the Sonoran Desert of Mexico. A wealth of background information on this model system has already been obtained including data on the ecology and genetics of the fruit flies and identification and characterization of the toxic chemicals that the cacti produce. The experiments outlined in this proposal will establish a connection between the mixed-function oxidase enzymes in these insects and their tolerance to the poisonous chemicals in the cactus plants. This is a necessary first-step in a long-term study of the ecological and evolutionary genetics of the genes which produce MFO enzymes in insects. Understanding this system could be an important contribution to the development of more effective insecticides.