Trpm5 is a calcium-activated cation channel expressed selectively in taste receptor cells. A previous study reported that mice with an internal deletion of Trpm5, lacking exons 15-19 encoding transmembrane segments 1-5, showed no taste-mediated responses to bitter, sweet, and umami compounds. We independently generated knockout mice null for Trpm5 protein expression due to deletion of Trpm5's promoter region and exons 1-4 (including the translation start site). We examined the taste-mediated responses of Trpm5 null mice and wild-type (WT) mice using three procedures: gustatory nerve recording [chorda tympani (CT) and glossopharyngeal (NG) nerves], initial lick responses, and 24-h two-bottle preference tests. With bitter compounds, the Trpm5 null mice showed reduced, but not abolished, avoidance (as indicated by licking responses and preference ratios higher than those of WT), a normal CT response, and a greatly diminished NG response. With sweet compounds, Trpm5 null mice showed no licking response, a diminished preference ratio, and absent or greatly reduced nerve responses. With umami compounds, Trpm5 null mice showed no licking response, a diminished preference ratio, a normal NG response, and a greatly diminished CT response. Our results demonstrate that the consequences of eliminating Trmp5 expression vary depending upon the taste quality and the lingual taste field examined. Thus, while Trpm5 is an important factor in many taste responses, its absence does not eliminate all taste responses. We conclude that Trpm5-dependent and Trpm5-independent pathways underlie bitter, sweet, and umami tastes.