Several recent experiments demonstrate the presence of an essential negatively charged acid group within sodium channels. Sodium permeability titrates away at low pH as if controlled by an acid with a voltage-dependent apparent pKa in the range between 5 and 6. The alkali ion permeability sequence of the channel is best explained by interactions between the cations and a strong negative charge in the channel. Block of sodium currents by a variety of metal and organic cations again points to a cation-coordinating site in the channel. The "blocking cations" and protons also oppose the bindings of tetrodotoxin and saxitoxin. The negative charge in the channel seems to be essential in selecting appropriate cations and in lowering their activation energy for permeation. The same charge seems to form part of the toxin receptor. At present this charged group is the chemical group known to be associated with sodium channels.--Hille B. An essential ionized acid group in sodium channels.