The blood-nerve barrier (BNB) is constituted by the perineurium and the endothelium of endoneurial microvessels. We investigated the age at which the vascular component of BNB function is established in the rat and the ultrastructural modifications accompanying changes in permeability. BNB permeability was assessed with injections of Evans blue albumin (EBA) and horseradish peroxidase (HRP) in rats of different ages. Sciatic nerve sections were studied using fluorescence and electron microscopy. Nerves from animals injected with EBA indicated that the BNB is not functional before 13 days of life but that its function is established by 16 days. These results were confirmed by electron microscope examination of nerve sections from animals injected with HRP, which showed clefts between the endothelial cells of endoneurial vessels in young rats. In rats over 18 days, these clefts were occluded by tight junctions, which prevented HRP from leaving the vessel lumen and conferred BNB function. Systematic morphometric analysis of nerves from different age groups allowed the establishment of baseline normal histologic neural development with age.