Horseradish peroxidase (HRP) was given to adult normal mice either intravenously or locally around the sciatic nerve. After varying time intervals the animals were sacrificed and fixed by whole body perfusion. The sciatic nerve was sampled and the distribution of peroxidatic activity was studied by light and electron microscopy. After both types of HRP administration the tracer was rapidly taken up by epi- and endoneurial cells with the ultrastructural features of macrophages. When increasing doses of HRP were injected intravenously a diffuse endoneurial extravasation was observed 30 min after the injection. It is concluded that a passage of HRP takes place over some endoneurial vessels. The nature and significance of endoneurial macrophages are discussed.