A key component to combating mosquito-borne illnesses is prevention from acquiring the disease. Current mosquito repellents, such as Permethrin and DEET, have been shown to be too costly and mosquitoes can eventually develop resistance to them. In this proposal, Olfactor Laboratories Inc. (OLI) supports the development of novel, spatial, non-insecticidal mosquito repellents for commercial and residential use around the world. Based upon the work of Dr. Anandasankar Ray of the University of California, Riverside (UCR), who demonstrated that the highly conserved carbon dioxide receptor in mosquitoes can be activated or inhibited by small molecules, OLI has identified over 80 molecules which have been approved for use by the FDA for use as flavors and fragrances that activate or inhibit the CO2 receptor, the primary host- seeking mechanism for mosquitoes. Through prolonged activation or inhibition of the carbon dioxide receptor, we will be able to provide repellency since mosquitoes will not be able to locate CO2 emissions from humans for a blood meal. With this suite of safe, carbon dioxide receptor activators and inhibitors, we are ready to begin behavioral testing in small area and flight assays. Apart from serving as a long-range attraction cue, CO2 has been shown to sensitize mosquitoes to skin odors and using small-area landing assays, we will be able to determine efficacy of the compounds when skin odor is present. Another key assay will be the flight assays, consisting of pre-exposure and co-exposure flight assays. Pre-exposure assays will help determine dose-dependent and duration efficacy while co-exposure flight assays will determine repellency when in direct competition with CO2. Individual odors or blends of odors with a repellency of at least 80% will proceed to Phase II testing which will include large observation chambers and semi-field trials. Through this work, we will be able to develop active ingredients for use in novel, spatial, non-insecticidal mosquito repellents to provide an important new tool for disease prevention.