The results of intra-arterial injections in cats under dial anesthesia indicate that nerve structures can be stimulated by neutral solns. of various types. Chlorides of Li, Na, caesium, Mg, Ca, and Sr excite pain-elements only when the total salt concn. approaches 1/2-molar. Moreover, in the absence of salts of Mg, Ca or Sr, hypotonic solns. such as distilled water or 0.3% NaCl stimulate both motor and sensory elements. Similarly, stimulation occurs when the nerve-structures are exposed to isotonic solns. containing certain ions, notably K, rubidium and Ba. The presence of salts of Mg, Ca and Sr, however, prevents stimulation of either motor or sensory nerve-elements by hypotonic solns. or by solns. containing the ions of K, Rb or Ba. These observations suggest that permeability of the cell-membrane may apply to the stimulation of peripheral nerve-elements subserving pain-sensibility in the intact mammalian body. Interpreted thus, hypertonic solns. stimulate by shrinking the nerve-structures, whereas the excitation by hypotonic solns. results from swelling. Low concs. of those ions which readily penetrate the nerve-membrane, e.g., K and Rb ion, give rise to stimulation. In contrast, ions to which the nerve membrane is relatively impermeable (Li, Na, Cs, etc.) fail to stimulate except in solns. so conc. as to exert a marked osmotic effect. Salts of Mg, Ca and Sr, according to this interpretation, are analgesic like narcotics by their protection of the nerve-membrane against penetration by stimulating agents. It has been suggested that under abnormal conditions substances which escape from injured cells into the intercellular fluids may accumulate in conc. sufficient to affect pain-endings. The results indicate that ability to penetrate the cell-membrane may be a useful criterion in the identification of such substances. The facts that K diffuses from injured cells to accumulate in inflammatory fluids, and that the K ion can penetrate nerve-structures and give rise to stimulation are of interest.