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Many excitable tissues are able to develop action potentials in the absence of any salt of univalent cation in the external medium. Osterhout and his associates' have shown that Nitella cells, which have been rendered inexcitable by prolonged immersion in distilled water, regain their excitability when calcium salts are added to the external medium. Fatt and Katz,2 Hagiwara, Chichibu, and Naka,3 and others have demonstrated that crustacean muscle fibers can produce large action potentials in media containing only salts of divalent cations. Frog ventricles4 and nerve cells in frog dorsal root ganglia5' 6 also are known to remain excitable in the absence of any univalent cations in the surrounding fluid medium. In contrast to the excitable systems stated above, it is generally believed that the squid giant axon requires sodium salts or other univalent cation substitutes for sodium in the external medium to maintain excitability. This article describes a series of observations demonstrating that under intracellular perfusion,7 8 squid giant axons are capable of developing large action potentials in the absence of univalent cations in the external medium. In previous articles from this laboratory,8' 9 detailed description has been made of the order of "favorability" of various inorganic and organic salts in the intracellular perfusion fluid. It has been shown that the common univalent cations form the following order of (decreasing) favorability:

Excitability of squid giant axons in the absence of univalent cations in the external medium.