Gustatory afferent fibers receiving taste signals from corresponding taste bud cells store transmitters such as glutamate and calcitonin gene‐related peptide (CGRP). However, to date, the effect of CGRP on signal processing in taste buds is not well understood.In this study, we characterized metabotropic CGRP receptors that appear to underlie the postulated efferent transmission present on taste cells. Specifically, we reported that Fura 2 loaded mouse vallate taste cells showed Ca2+ mobilization in responses to a low concentration of CGRP (0.1 μM). The findings were that a significant fraction of Presynaptic (Type III) taste bud cells (53%) responded to CGRP, and that only few Receptor (Type II) taste cells (5%) were activated by this transmitter. CGRP8‐37, a CGRP receptor antagonist, reversibly abolished Ca2+ responses and elucidated the actions of CGRP. Removing extracellular Ca2+ had no effect on responses evoked by CGRP stimulation. In marked contrast, applying 1 μM thapsigargin, a SER Ca‐ATPase inhibitor, or 10 μM U73122, a PLC blocker, eliminated Ca2+ responses, suggesting that CGRP stimulation triggered PLC/IP3‐mediated release of Ca2+ from intracellular stores. Using CHO/biosensor cells expressing 5‐HT2C receptors, we also measured taste‐evoked transmitter release from taste buds. Consistent with these results, applying CGRP caused taste buds to secrete 5‐HT, a Presynaptic (Type III) taste cell transmitter. Biosensor responses evoked by stimulating taste buds were reversibly blocked by mianserin, a 5‐HT2C receptor antagonist, verifying that the signals arose from serotonin. We conclude that CGRP as an efferent transmitter may act via serotonergic mechanisms to modulate the final output of taste signaling. Grant Funding Source: Supported by SIUSOM Startup Funds.