Reactive gliosis, a general response to injury in the central system grey and white matter, represents a serious obstacle to axonal regeneration in mammals. In culture, myelin-free plasma membranes from normal rat brain tissue promoted neurite outgrowth, whereas myelin-free membranes purified from injured tissue were inhibitory. The inhibitory activity could be solubilized by detergent, was sensible to glycosaminoglycan lyase digestion and eluted with an apparent molecular weight of 160-220 kDa in gel filtration chromatography. When presented as a surface-bound molecule, the inhibitor prevented neurite initiation; when added in a soluble form to growing neurites, it induced their retraction. These results provide cellular and molecular evidence supporting the classical view that, in the mammalian central nervous system, damage-evoked gliosis correlates with the expression of molecules capable of preventing neurite outgrowth.