The nerve growth factor protein is necessary for the development and maintenance of a differentiated state by peripheral nervous system neurons. The SK-N-SH-SY-5Y (SY5Y) is a nearly diploid, thrice subcloned cell line of human neuroblastoma. In the undifferentiated state (SY-5Y) appear in culture as undifferentiated neuroblasts whose plasma membranes are electrically not excitable by any of a number of techniques. Undifferentiated SY-5Y possess few axonal processes per cell (less than 1%), are highly susceptible to the toxic effects of 6-hydroxydopamine. SY-5Y in the undifferentiated state have high levels of dopamine beta hydroxylase and tyrosine hydroxylase and barely detectable levels of choline acetyltransferase. Exposure to murine NGF elicits production of neurites, electrical excitability, protection from 6-hydroxydopamine killing and complete but reversible cessation of cellular proliferation with a concomitant stimulation of protein synthesis. This provides for a useful model system with which to dissect the molecular aspects of neuronal differentiation peculiar to the nerve growth factor response. In particular we are interested in the mechanism by which nerve growth factor confers protection to the cells from 6-hydroxydopamine toxicity. Given that treatment of SY5Y with dibutyl cyclic AMP does elicit neurite outgrowth and its concomitant property, membrane excitability, it was of interest that the toxic effects of 6-hydroxydopamine were significantly enhanced and no cellular protection ensued.