Amphibian skin secretion is a rich source of biological compounds. Histological, morphometrical, functional, and protein biochemical methods were used to understand the role of skin glands in the tail of the red-legged salamander (Plethodon shermani), an emerging organismal model for the physiology and evolution of pheromonal communication. Individual granular glands were approximately three times larger in the dorsal tail skin compared to the ventral tail skin. Dorsal tail granular glands emptied when animals were handled to induce release of noxious/sticky substances. Ventral tail granular glands emptied during scent marking. Granular glands in both dorsal and ventral tail skin rapidly enlarged when animals were placed on a clean substrate. Histological study of tail skin identified a subset of ventral granular glands that stained differently from dorsal granular glands. Protein analysis of acetylcholine chloride extracts of dorsal tail skin and ventral tail skin revealed differences in the protein content released by glands in these tail regions. Together, these data suggest that the dorsal granular glands secrete noxious/sticky substances putatively involved in predator defense and the ventral granular glands secrete products possibly involved in scent marking. Future studies will examine behavioral responses to dorsal and ventral tail skin secretions in order to better understand their role in chemical defense and chemosensory communication.