The expression of two vesicular glutamate transporters (VGLUTs), VGLUT(1) and VGLUT(2), was studied with immunohistochemistry in lumbar dorsal root ganglia (DRGs), the lumbar spinal cord and the skin of the adult mouse. About 12% and 65% of the total number of DRG neuron profiles (NPs) expressed VGLUT(1) and VGLUT(2), respectively. VGLUT(1)-immunoreactive (IR) NPs were usually medium- to large-sized, in contrast to a majority of small- or medium-sized VGLUT(2)-IR NPs. Most VGLUT(1)-IR NPs did not coexpress calcitonin gene-related peptide (CGRP) or bound isolectin B4 (IB4). In contrast, similar to 31% and similar to 42% of the VGLUT(2)-IR DRG NPs were also CGRP-IR or bound IB4, respectively. Conversely, virtually all CGRP-IR and IB4-binding NPs coexpressed VGLUT(2). Moderate colocalization between VGLUT(1) and VGLUT(2) was also observed. Sciatic nerve transection induced a decrease in the overall number of VGLUT(1)- and VGLUT(2)-IR NPs (both ipsi- and contralaterally) and, in addition, a parallel, unilateral increase of VGLUT(2)-like immunoreactivity (LI) in a subpopulation of mostly small NPs. In the spinal cord, strong VGLUT(1)-LI was detected, particularly in deep dorsal horn layers and in the ventral horns. VGLUT(2)-LI was abundant throughout the gray spinal matter, 'radiating' into/from the white matter. A unilateral dorsal rhizotomy reduced VGLUT(1)-LI, while apparently leaving unaffected the VGLUT(2)-LI. Transport through axons for both VGLUTs was confirmed by their accumulation after compression of the sciatic nerve or dorsal roots. In the hind paw skin, abundant VGLUT(2)-IR nerve fibers were observed, sometimes associated with Merkel cells. Lower numbers of VGLUT(1)-IR fibers were also detected in the skin. Some VGLUT(1)-IR and VGLUT(2)-IR fibers were associated with hair follicles. Based on these data and those by Morris et al. [Morris JL, Konig P, Shimizu T, Jobling P, Gibbins IL (2005) Most peptide-containing sensory neurons lack proteins for exocytotic release and vesicular transport of glutamate. J Comp Neurol 483:1-16], we speculate that virtually all DRG neurons in adult mouse express VGLUTs and use glutamate as transmitter. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.