Perineurial cells are of mesenchymal origin and form the perineurium. The perineurium plays an important role in maintaining the integrity of the internal peripheral nerve environment by creating a physical barrier that, under physiologic condition, limits the entry of biologically active proteins, infectious agents, and blood-borne cells into the nerve bundles. The perineurial cells (PNC) are characterized by distinct ultrastructural features, including non-branching thin cytoplasmic processes coated by an external lamina and joined at their ends by a tight junction, few organelles, actin and vimentin filaments, and numerous pinocytotic vesicles. PNC are initially recruited from the surrounding mesenchyme to form a loose, permeable sheath around axons and Schwann cells, where they are separated by the extracellular matrix. These cells later undergo a mesenchymal-to-epithelial transition to form tight junctions and organize into the perineurium. PNC are immunoreactive for vimentin and epithelial membrane antigen but not for the Schwann cell marker S-100.