Until now the only reported effect of depolarization on the intracellular pH (pH_i) of excitable cells is an acidification of the cell cytoplasm^1,2. It seems unlikely that this could be a direct effect of membrane potential because pH_i is known to be regulated by an electroneutral mechanism^3,4 and in most cells H⁺ ions are not in equilibrium with the membrane potential (E_m). In any case the membrane conductance to H⁺ ions would be expected to be small because they are at such low concentrations on either side of the cell membrane. But it is possible that the H⁺ ion permeability of the membrane increases on depolarization just like that of other ions in the bathing medium (Na⁺, K⁺ and Ca²⁺ for example). To test this idea we have made pH_i measurements on molluscan neurones under voltage-clamp. Our findings, presented here, provide evidence for a large increase in H⁺ ion permeability in depolarized cells. We suggest that this increase in proton conductance may be the basis for the ‘nonspecific’ currents previously described in perfused molluscan neurones^5,6 and we assess the physiological significance of this newly discovered pathway.