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 Ca(2+)-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 microM; the [Ca2+]i at the release sites during depolarizations was estimated to be 3-10 microM. 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.