A tissue culture model was designed to characterize the ability of axonal membranes and detergent extracts of membranes to down regulate nerve growth factor (NGF) receptors on the Schwann cell surface. The findings establish that (i) axons from intact neurons, as well as axonal membrane fragments, and extracts of these axons can down regulate Schwann cell NGF receptor number, (ii) central, as well as peripheral, axons have the ability to affect Schwann cell NGF receptor expression, (iii) cross-species reactivity is evident with this phenomenon, (iv) physical contact is necessary for axons to down regulate Schwann cell NGF receptor, (v) the response of axons is glial specific, and (vi) soluble, truncated NGF receptors elaborated by Schwann cells are also down-regulated by axon components. © 1990.