SINCE Lorente de No1 found that a group of small axons (“Et fibres”) in the frog are able to conduct prolonged action potentials when the external sodium is replaced by certain quaternary ammonium ions, special attention has been directed to the effects of these compounds on other excitable tissues. Fatt and Katz2 observed that the electrical responses of crustacean muscle fibres are maintained and even intensified when choline, tetramethylammonium, tetraethylammonium or tetrabutylammonium ions are substituted for the sodium in the external medium. No other excitable tissue, however, has been reported to show active responses after complete replacement of sodium by these ions. Choline, in particular, has repeatedly been used as an ‘inert’ osmotic substitute in experiments on sodium depletion in the extracellular spaces. At low concentrations, for example, 10–20 per cent replacement of sodium, tetraefchylammonium lengthens the falling phase of the action potential of crustacean nerve3 and of frog twitch muscle4. The intracellular injection of tetraethylammonium into the giant axon of the squid prolongs the duration of the action potential5. In frog nerve fibres, the enhancement of the negative after-potential produced by addition of tetraethylammonium to the Ringer's solution is more prominent in the terminal endings than in the nodes6, suggesting that quaternary ammonium ions might act in different degrees on the various parts of the neurone.