The heterogeneous contents of the CNS interstitial clefts and the configuration of their astrocytic walls may be regionally variable. Astrocytic processes of the glia limitans, in normal midbrain and in astroglial scars, form thin, parallel, concentric sheets comprising the walls of narrow interstitial clefts. There is a critical thickness of about 20 to 30 nm, below which astrocytic cell process or those of the fibroblast-like cells in the meninges, do not invaginate to form transcytotic vesicles. Large hydrophilic solutes cannot, therefore, pass across the thin portion of a cell process. Consequently, (a) the diffusion and convection paths of interstitial fluid and solutes are lengthened, (b) a solute will remain within the interstitial cleft between thin lamellae for a relatively long time and (c) if a ligand does bind to its receptor on the thin process's cell membrane, there can be no receptor-mediated transcytosis at that site. Interstitial clefts, themselves, vary in size, shape and content, including extracellular matrix and basal lamina. A common constituent of basal lamina and extracellular matrix, presumably including that at ependymal, astroglial and endothelial interfaces of the CNS, is heparan sulfate proteoglycans. As in other organs, these proteoglycans may store growth factors, growth inhibitors, cytokines and other modulators which can then be released enzymatically during, e.g., regeneration. Exogenous heparan sulfate proteoglycan might serve as a natural, intermittent-release matrix for delivery of trophic factors.