Until now the only reported effect of depolarization on the intracellular pH (pHi) of excitable cells in an acidification of the cell cytoplasm. It seems unlikely that this could be a direct effect of membrane potential because pHi is known to be regulated by an electroneutral mechanism and in most cells H+ ions are not in equilibrium with the membrane potential (Em). 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 depolarization just like that of other ions in the bathing medium (Na+, K+ and Ca2+ for example). To test this idea we have made pHi 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 and we assess the physiological significance of this newly discovered pathway.