The protective barriers of the sciatic nerve in protein deprived and normal rats have been studied. Horseradish peroxidase (HRP) was applied extra-neurally in rats aged between 4 and 26 weeks. The spread of the tracer was investigated 2 h, 24 h, and 3 days after application. Passage of tracer into the endoneurium was found in all rats but decreased with age. Within the endoneurium, HRP was phagocytized by normally occurring endoneurial histiocytes, which constitute part of the protective barrier system of peripheral nerves. The functional development of the nerve protective barriers was retarded in protein deprived rats. Observations made in this study support the concept of a transperineurial vesicular transport of macromolecules.