Axons often respond to lesions by spontaneous sprouting which, in the PNS, can be followed by elongation over long distances. In contrast, in the CNS, regenerative axon growth in most fibre systems subsides after 0.5-1.0 mm. The observation that an identical situation can be found in tissue culture in the presence of trophic factors argued for the existence of inhibitory mechanisms within the CNS tissue. Detailed cell biological and biochemical studies have provided evidence for two membrane proteins localized selectively in oligodendrocytes and CNS myelin and which exert a powerful inhibitory effect on neurite growth. Antibodies raised against these neurite growth inhibitors (NI-35 and NI-250) and applied to rats with complete transections of the corticospinal tract (CST) resulted in CST axon regeneration over five to ten mm from the lesion site within two to three weeks. Analogous results were obtained in rats lacking myelin and oligodendrocytes in the spinal cord. During development, the 'fuzzy' appearance of the CST grown in the absence of oligodendrocytes or in the presence of anti-inhibitor antibodies indicates a boundary and guidance function of these inhibitors for late growing CNS tracts.