Roughly 45-50% of human adults with otherwise normal olfactory abilities cannot smell high concentrations of androstenone, a naturally occurring compound, while others can detect an odor at less than 200 parts per trillion in air. We have determined that this extreme variation in sensitivity has a significant genetic component. However, sensitivity to androstenone is not immutable. There are changes with age, and more striking, extensive exposure to the odorant appears to induce an ability to detect it. In this proposal we describe a series of human and animal model studies designed to explore the interaction between the genetic influence on ability to detect an odor and the effects of experience with that odor. Using standard psychophysical methods, we propose to explore the nature of the changes in human sensitivity to androstenone which is induced by exposure to the odorant as well continue our studies on developmental factors affecting sensitivity. We also propose to continue to work with genetically inbred strains of mice to verify that we have isolated a model for insensitivity to androstenone and study it using standard genetic methods, to estimate the number of genetic loci involved in regulating sensitivity to selected odorants, and to determine whether we can increase sensitivity to odorants in mice found to be insensitive to them. These studies will produce fundamental information on mammalian olfaction by providing an integrated study of factors (genetic, developmental and experimental) that may influence sensitivity to odorants. While much progress has been made in understanding sensory systems through the use of genetic methods, these approaches have not been fully exploited in the study of nasal chemoreception. Indeed, olfaction is one of the least understood of the classical sensory systems; mechanisms of reception, transduction, and coding have yet to be clearly elucidated. Studies of people and other animals having selective deficits may contribute to our understanding of olfaction much like studies of color-blind individuals have contributed to our understanding of chromatic vision.