The PC12 clone is a line of rat pheochromocytoma cells which undergoes neuronal differentiation in the presence of nerve growth factor (NGF) protein. In the absence of NGF, PC12 cells are electrically inexcitable, while after several weeks of NGF treatment, they develop sodium action potentials. The number and density of sodium channels on PC12 cells before and after treatment with NGF were estimated by measuring the binding of [3H]saxitoxin ([3H]STX). The data indicate that [3H]STX binding increases in the NGF-treated cells by 15- to 20- fold per cell, 3- to 10-fold per mg of protein, and an estimated 7-fold per unit area of membrane. The kinetic properties for [3H]STX binding are unchanged, however, by NGF treatment. A Hodgkin-Huxley analysis (Hodgkin, A. L., and A. F. Huxley (1952) J. Physiol. (Lond.) 117: 500– 544) suggests that the estimated density of sodium channels in NGF- untreated PC12 cells is sufficient to explain their lack of excitability. On the other hand, the estimated channel density on the NGF-treated cells (30 to 50/micrometers 2) is comparable to that in other excitable systems. Thus, the development of excitability in PC12 cells in response to NGF could be due to the induction of sodium channel synthesis.