SFVERAL lines of evidence suggest that both sweet and bitter tastes are transduced via receptors coupled to heterotrimeric guanine-nucleotide-binding proteins (G proteins) (reviewed in refs 1, 2). Gustducin is a taste receptor cell (TRC)-specific G protein that is closely related to the transducins(3). Gustducin and rod transducin, which is also expressed in TRCs (ref. 4), have been proposed to couple bitter-responsive receptors to TRC-specific phosphodiesterases to regulate intracellular cyclic nucleotides(2-5). Here we investigate gustducin’s role in taste transduction by generating and characterizing mice deficient in the gustducin alpha-subunit (alpha gustducin). As predicted, the mutant mice showed reduced behavioural and electrophysiological responses to bitter compounds, whereas they were indistinguishable from wild-type controls in their responses to salty and sour stimuli. Unexpectedly, mutant mice also exhibited reduced behavioural and electrophysiological responses to sweet compounds. Our results suggest that gustducin is a principal mediator of both bitter and sweet signal transduction.