Inhaled airborne irritants elicit sensory responses in trigeminal nerves innervating the nasal epithelium, leading to protective reflexes. The sensory mechanisms involved in the detection of odorous irritants are poorly understood. We identified a large population of solitary chemosensory cells expressing the transient receptor potential channel M5 (TRPM5) using transgenic mice where the promoter of TRPM5 drives the expression of green fluorescent protein (GFP). Most of these solitary chemosensory cells lie in the anterior nasal cavity. These GFP-labeled solitary chemosensory cells exhibited immunoreactivity for synaptobrevin-2, a vesicle-associated membrane protein important for synaptic transmission. Concomitantly, we found trigeminal nerve fibers apposed closely to the solitary chemosensory cells, indicating potential transmission of sensory information to trigeminal fibers. In addition, stimulation of the nasal cavity with high concentrations (0.5-5 mM) of a variety of odorants elicited event-related potentials (ERPs) in areas rich in TRPM5-expressing solitary chemosensory cells. Furthermore, odorous chemicals and trigeminal stimuli induced changes in intracellular Ca(2+) levels in isolated TRPM5-expressing solitary chemosensory cells in a concentration-dependent manner. Together, our data show that the TRPM5-expressing cells respond to a variety of chemicals at high exposure levels typical of irritants and are positioned in the nasal cavity appropriately to monitor inhaled air quality.