Recent studies have demonstrated receptors in the nervous system for transferrin, the iron binding and transport protein in the blood. This study using immunohistochemistry at the light and electron microscopic levels demonstrates that transferrin (Tf) is found predominantly in oligodendrocytes in both the gray and white matter of the cerebral cortex, cerebellum and spinal cord. Within the cerebral cortex, layer V has more Tf-labeled cells than the other cortical layers. In the spinal cord, lamina VII has the highest density of Tf-positive cells. Based on location, 3 types of oligodendrocytes can be described: perineuronal, interfascicular and perivascular. In addition to oligodendrocytes, endothelial cells and possibly some neuronal membranes of layer V pyramidal and anterior horn cells label with Tf antiserum. Ultrastructurally, Tf reaction product is homogeneously distributed throughout the perinuclear cytoplasm of both oligodendrocytes and endothelial cells. The importance of iron in motor and behavior function is well established although the mechanism of action of iron in the CNS is not well understood. The presence of Tf in oligodendrocytes implies that these neuroglia are involved in iron mobilization and storage in the CNS. Stored quantities of iron and the ability to mobilize the iron through stored transferrin may be the reason for the extreme dietary restrictions necessary to induce iron-deficient CNS disorders.