Until recently, dietary fat was considered to be tasteless, and its primary sensory attribute was believed to be its texture (; ). However, a number of studies have demonstrated the ability of components in fats, specifically free fatty acids, to activate taste cells and elicit behavioral responses consistent with there being a taste of fat. Here we show for the first time that long-chain unsaturated free fatty acid, linoleic acid (LA), depolarizes mouse taste cells and elicits a robust intracellular calcium rise via the activation of transient receptor potential channel type M5 (TRPM5). The LA-induced responses depend on G-protein-phospholipase C pathway, indicative of the involvement of G-protein-coupled receptors (GPCRs) in the transduction of fatty acids. Mice lacking TRPM5 channels exhibit no preference for and show reduced sensitivity to LA. Together, these studies show that TRPM5 channels play an essential role in fatty acid transduction in mouse taste cells and suggest that fatty acids are capable of activating taste cells in a manner consistent with other GPCR-mediated tastes.