Previous studies have suggested that nicotine may have beneficial actions in neurodegenerative disease models. The purpose of the experiments described in this study was to determine whether the long lasting and beneficial effects of nicotine observed previously could be expressed through actions upon nerve growth factor (NGF) receptors. Using a differentiated PC-12 neuronal cell model, we have detected an increase in expression of cell surface NGF receptor protein after acute exposure to nicotine in the micromolar range. In addition, we have also observed a persistent effect upon NGF receptor expression which lasted even after nicotine (nanomolar range) was removed from the tissue culture medium. This increase in cell surface NGF receptor protein was blocked in the presence of mecamylamine, indicating that this effect is likely nicotinic receptor mediated. These results are consistent with the hypothesis that the lasting and beneficial actions of nicotine previously observed in vivo may involve an indirect effect upon the level of neuronal cell surface NGF receptor expression. Our observations offer one possible mechanism for a potential neurotrophic effect of nicotine.