We report the cloning of a Distal-less-like gene (PwDlx-3) and its pattern of expression during embryonic development and adult tail regeneration in the urodele Pleurodeles waltl. Using RT-PCR and in situ hybridization experiments we determined that, during regeneration, PwDlx-3 is expressed in the epidermis, the cells associated with muscle masses and in the ventrolateral parts of the ependymal tube. PwDlx-3 localization in the muscle masses and in cells of the ependymal tube, which give rise during regeneration to the ventral roots and the spinal ganglia, suggests that this gene might be expressed in cells which have some neural crest cell potentialities. PwDlx-3 is the first homeobox gene shown to be expressed in the regenerating spinal cord but not in the adult one and could thus be involved in the regeneration of the nervous system.