Denervation in man often results in shiny, dry, thin skin. A previous study has shown that the epidermis of glabrous skin in the rat becomes approximately 40% thinner within 1 week following sciatic nerve transection, but which nerve fiber type or types influence epidermal thickness is unknown. In this study, we compared the effects on the epidermis of selective sensory, motor, and sympathetic denervation. Protein gene product 9.5 and calcitonin gene-related peptide immunocytochemical staining were used to determine the extent of denervation of epidermis, dermis, and sweat glands in the footpads. Epidermal thickness of the glabrous plantar skin of the foot was measured to verify the specificity and reliability of each animal model, the relevant regions of the peripheral nervous system were examined by light or electron microscopy or both. Epidermal thickness decreased significantly following sciatic nerve transection (58% of control, P <0.05) and dorsal root ganglionectomy (59%; P <0.05). The thickness also decreased following lumbar ventral rhizotomy (61%; P <0.01), destruction of lumbar spinal motor neurons (66%; P <0.05), and botulinum toxin-induced paralysis of the tibialis anterior and gastrocnemius muscles (70%; P <0.05). A slight decrease followed dorsal rhizotomy (84%; P <0.01). In contrast, no significant alterations in epidermal thickness were detected following sham operation and sympathectomy. Epidermal thinning was paralleled by reductions in the amounts of transcripts for glyceraldehyde-3-phosphate dehydrogenase and β-actin. These results suggest that selective loss of both sensory and motor fibers to the hind limb can contribute to reducing epidermal thickness in rat foot glabrous skin.