Abstract We have investigated the Ca2+ dependence of vesicular secretion from the soma of dorsal root ganglion (DRG) neurons, which secrete neuropeptides by exocytosis of dense-core vesicles. In patch-clamped somata of rat DRG neurons, we found a depolarization-induced membrane capacitance increase (DeltaCm) in the absence of extracellular Ca2+ and in the presence of a Ca2+ chelator (BAPTA) in the intracellular solution. Depletion of internal Ca2+ stores by thapsigargin in the Ca2+-free bath also did not block the DeltaCm, indicating that Ca2+ release from internal Ca2+ stores may not have been involved. Furthermore, the Ca2+-independent DeltaCm was blocked by whole-cell dialysis with tetanus toxin and was accompanied by pulsatile secretion of false transmitters, as detected by amperometric measurements. These results indicate the existence of Ca2+-independent but voltage-dependent vesicular secretion (CIVDS) in a mammalian sensory neuron.