Gustducin, a transducin-like guanine nucleotide-binding regulatory protein (G protein), and transducin are expressed in taste receptor cells where they are thought to mediate taste transduction. Gustducin and transducin are activated in the presence of bovine taste membranes by several compounds that humans perceive to be bitter. We have monitored this activation with an in vitro assay to identify compounds that inhibited taste receptor activation of transducin by bitter tastants: AMP and chemically related compounds inhibited in vitro responses to several bitter compounds (e.g., denatonium, quinine, strychnine, and atropine). AMP also inhibited behavioral and electrophysiological responses of mice to bitter tastants, but not to NaCl, HCl, or sucrose. GMP, although chemically similar to AMP, inhibited neither the bitter-responsive taste receptor activation of transducin nor the gustatory responses of mice to bitter compounds. AMP and certain related compounds may bind to bitter-responsive taste receptors or interfere with receptor-G protein coupling to serve as naturally occurring taste modifiers.