In terrestrial vertebrates, olfactory sensations are normally produced by airborne odorants which pass through the nose during breathing, sniffing, and eating. However, in hematogenic or intravascular olfaction, odorous sensations are elicited by odorants carried in the bloodstream. For many years it was believed that blood-borne odorants are transported to the olfactory receptor cells only in the exhaled air after diffusing out of the bloodstream in the lungs. However, we recently have shown that they also appear to reach the receptors by diffusing out of the bloodstream in the nasal capillary bed. This latter route has potential practical applications as a unique means for delivering odorants in the clinic and lab. One such use would be the injection of odorants into the bloodstream to test olfactory function in patients with blocked nasal airflow. The fundamental importance of intravascular olfaction lies in the effects that odorants in the bloodstream have on the olfactory system. Odorants are known to enter the bloodstream after the ingestion of food and beverages, inhalation of pollutants, injection of volatile drugs, contact exposure to solvents, and many disease states. These bloodborne odorants may create an internal odor milieu which stimulates the olfactory system, altering olfactory perception of the external world and affecting olfactory mediated behaviors such as feeding. The objectives of the present four-year proposal are to investigate: (1) the nature and sensitivity of olfactory responses to intravascular delivery of odorants; (2) the ability of vapor phase and intravascular odorants to modulate olfactory sensitivity to each other; (3) the responses of rat olfactory receptor cells to intravascular odorants when lung air is allowed to pass through the nose as in the normal animal or is vented to the outside as in the tracheotomized animal; (4) using gas chromatographic techniques, how injected odorants partition between the blood, nasal cavity and lung gases; and (5) the sensitivity of trigeminal chemoreceptors to intravascular odorants.