Reactive‘ astrocytes and ‘activated’ microglial cells are the major cellular components of gliotic tissue, one of the most serious obstacles to axonal regeneration in mammalian central nervous system grey and white matter. The appearance of reactive glial cells after a lesion in the CNS correlates with the expression of molecules, like proteoglycans, capable of preventing neurite outgrowth. Co-cultures of embryonic neurones with glial cells and glial cell lines, that might share characteristics with reactive astrocytes and microglial cells, show that while cultured astrocytes promote neurite outgrowth, plasma membranes of C6 glioma and microglial cells express neurite inhibitory activites with proteoglycan-like characteristics, similar to those expressed by the gliotic tissue associated inhibitors. These results suggest that in vivo microglial cells might be at least one of the sources of proteoglycans with neurite outgrowth inhibitory properties.