Avian intrapulmonary chemoreceptors (IPC) are vagal respiratory afferents that are inhibited by high lung PCO₂ and excited by low lung PCO₂. Previous work suggests that increased CO₂ inhibits IPC by acidifying intracellular pH (pH_i), and that pH_i is determined by a kinetic balance between the rate of intracellular carbonic anhydrase-catalyzed CO₂ hydration/dehydration and transmembrane extrusion of acids and/or bases by various exchangers. Here, the role of amiloride-sensitive Na⁺/H⁺ exchange (NHE) in the IPC CO₂ response was tested by recording single-unit action potentials from IPC in anesthetized ducks, Anas platyrhynchos. For each of the IPC tested, blockade of the NHE using dimethyl amiloride (DMA) elicited a marked (>50%) dose-dependent decrease in mean IPC discharge (P < 0.05), suggesting that NHE is important for pH_i regulation and CO₂ transduction in IPC. In addition, activation of the NHE using 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulated 6 of the 7 IPC tested, although the overall effect was not statistically significantly (P = 0.07). Taken together, these findings suggest that CO₂ transduction in IPC is dependent on transmembrane NHE although it is likely to be much slower than carbonic anhydrase catalyzed hydration-dehydration of CO₂.