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Toads obtain water by absorption across their skin. When dehydrated, desert toads exhibit stereotyped hydration behavior in which they press their ventral skin onto a moist surface. However, dehydrated toads avoid surfaces moistened with hyperosmotic NaCl and KCl solutions (Hoff KvS, Hillyard SD. 1993. J. Exp. Biol. 183:347-351). We have studied neural mechanisms for this avoidance with physiologic, behavioral, and morphologic approaches. Spinal nerves innervating the ventral skin could be stimulated by exposure to a hyperosmotic NaCl solution applied to the outer surface of the skin. This neural response occurred with much longer latency than to mechanical stimulation and could be reduced by amiloride, a blocker for Na+ channels known to be responsible for epithelial ion transport and salt taste transduction. In behavioral experiments, avoidance of a NaCl solution was also reduced by adding amiloride to the solution, suggesting involvement of amiloride-sensitive Na+ channels for detecting the hyperosmotic salt solution. Neural tracing with fluorescent dye revealed spinal nerve endings and connections to putative receptor cells, both located in the deeper layer of the epidermis. Either of these or both may be associated with the transduction of Na+ flowing into the skin. The ability of toads to detect hyperosmotic salt solutions in their environment reveals a previously unknown chemosensory function for spinal nerves in anuran amphibians. (C) 1999 Wiley-Liss, Inc.