Using capacitance measurements and the single-cell immunoblot assay to study secretion in dorsal root ganglion neurons, we found that the somata underwent robust exocytosis upon depolarization and released substance P, in response to KCl stimulation. The parallel changes between capacitance responses and intracellular Ca²⁺ concentration ([Ca²⁺]_i) at different membrane potentials and the inhibition of exocytosis by Ca²⁺ chelators suggest that soma release is Ca²⁺-dependent. We also assessed the level of Ca²⁺ required for exocytosis by raising the average [Ca²⁺]_i with the Ca²⁺ ionophore, ionomycin. Capacitance changes were triggered by cytosolic Ca²⁺ > 0.6 μM; the [Ca²⁺]_i at the release sites during depolarizations was estimated to be 3–10 μM. These Ca²⁺ levels are similar to those obtained from neuroendocrine cells, but are at least 10 times lower than those required for transmitter release from nerve terminals.