Overton demonstrated in 1902 (13) that sodium ions are necessary to maintain the excitability of the nerve fibers, since (a) the nerve fibers become inexcitable if the concentration of sodium ions in their external medium is decreased below a certain value (about 0.012 ~) and (b) the excitability of the nerve fibers can be restored by increasing the external concentration of sodium ions. In recent years the role of sodium in nerve function has been analyzed by and by Gallego (3) with frog nerve, and by Hodgkin and Katz (5) with invertebrate nerve fibers.Overton also demonstrated that lithium ions can substitute for sodium ions in so far as they can restore the excitability of nerve fibers that have become inexcitable in a sodium-free medium; the restoring action of lithium ions, however, is only temporary since the continued presence of lithium ions in the external medium again renders the nerve fibers inexcitable. The ability of lithium ions to substitute for sodium ions has been confirmed by Hodgkin and Katz who worked with the giant axon of the squid.In this paper an analysis is made of the effect of lithium ions upon frog nerve deprived of sodium. It has been found that lithium ions can restore the excitability of fibers of fast conduction (A fibers in Erlanger and Gasser's classification, cf. Erlanger, 1) as well as the excitability of fibers of slow conduction (C fibers in Erlanger and Gasser's classification). The effect of lithium ions upon sodium-deficient B fibers has not been investigated. On the other hand, it has been found that lithium ions cannot substitute for sodium ions in other aspects of nerve function, as should be expected from the observation made by Overton that prolonged action of lithium ions renders the nerve fibers inexcitable, and from the observation made by Gallego and Lorente de N6 (4) that lithium ions when present in the external medium of the nerve fibers at a high concentration cause a depolarization of the nerve fibers.According to Overton (13) ammonium ions are not able to restore the excitability of nerve deprived of sodium. Reexamination of this question seemed desirable, however, because Overton worked only with fibers of the A group (motor fibers) while Lorente de N6 (8) has shown that a number of quaternary ammonium ions, which are not able to restore the excitability of A fibers, 227