The role of basolateral Na⁺-H⁺-exchanger isoform-1 (NHE-1) was investigated in neural adaptation of rat taste responses to acidic stimuli, by direct measurement of intracellular pH (pH_i) in polarized taste receptor cells (TRCs) and by chorda tympani (CT) taste nerve recordings. In TRCs perfused with CO₂/HCO₃^--free solution (pH 7.4), removal of basolateral Na⁺ decreased pH_i reversibly and zoniporide, a specific NHE-1 blocker, inhibited the Na⁺-induced changes in pH_i. The spontaneous rate of TRC pH_i recovery from NH₄Cl pulses was inhibited by basolateral zoniporide with a K_i of 0.33 mM. Exposure to basolateral ionomycin, reversibly increased TRC Ca²⁺, resting pH_i, and the spontaneous rate of pH_i recovery from an NH₄Cl pulse. These effects of Ca²⁺ on pH_i were blocked by zoniporide. In in vivo experiments, topical lingual application of zoniporide increased the magnitude of the CT responses to acetic acid and CO₂, but not to HCl. Topical lingual application of ionomycin did not affect the phasic part of the CT responses to acidic stimuli, but decreased the tonic part by 50% of control over a period of about 1 minute. This increased adaptation in the CT response was inhibited by zoniporide. Topical lingual application of 8-CPT-cAMP increased the CT responses to HCl, but not to CO₂, and acetic acid. In the presence of cAMP, ionomycin increased sensory adaptation to HCl, CO₂, and acetic acid. Thus, cAMP and Ca²⁺ independently modulate CT responses to acidic stimuli. While cAMP enhances TRC apical H⁺ entry and CT responses to strong acid, an increase in Ca²⁺ activates NHE-1, and increases neural adaptation to all acidic stimuli.