In an attempt to determine the chemosensory cues, if any, provided by fats in the oral cavity, we have performed patch-clamp recordings on isolated rat taste receptor cells during application of free fatty acids. Cis-polyunsaturated fatty acids, when applied extracellularly, inhibit delayed-rectifying K+ channels. In a subset of cells, these fatty acids also enhance inwardly rectifying K+ currents. Saturated, monounsaturated, and trans-polyunsaturated fatty acids have no significant effect on K+ currents. These effects do not involve activation of G protein-mediated pathways, including protein kinase C and protein kinase A, lipoxygenase pathways, cyclooxygenase pathways, or cytochrome P-450 pathways, consistent with direct effects on these ion channels or closely associated proteins. The net effect of fatty acids is to prolong stimulus-induced depolarizations of taste receptor cells, and we propose the effects on K+ channels represent the mechanism by which fats are detected by receptor cells in the oral cavity.