Capsaicin excites a subset of dorsal root ganglion (DRG) neurons by inducing an inward current. We have examined this inward current in response to high concentrations of protons in the external medium. The experiments were done in freshly dissociated DRG cells under whole-cell voltage-clamp conditions. The amplitude of the current evoked by capsaicin (200-300 nM) was increased with increasing concentrations of protons (pH 6.9-6.3). Increasing the acidification of the external medium from a physiological pH of 7.3 to 6.3 enhanced 7-fold the current induced by capsaicin (300 nM). Cells unresponsive to capsaicin in a physiological pH were also unresponsive to capsaicin in an acidic solution. There was a progressive decrease in the amplitude of the capsaicin-evoked current when the drug was repeatedly applied either at a physiological pH or an acidic pH of 6.3. Exposure of the cell to acidic solutions of capsaicin did not subsequently increase an evoked inward current when capsaicin was applied at a physiological pH nor did it lead to an inward current evoked by proton ions where there had been none. Our results suggest that increased proton concentrations in the extracellular medium could play an important modulatory role in the function of chemosensitive sensory neurons.