In the isolated parietal cell the following observations were made: gastrin led to an increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) even in the absence of medium Ca2+ and to transient membrane depolarization in both the absence of the medium Ca2+ and the fura-2-loaded cell. The incorporated Ca2+ chelator BAPTA inhibited the gastrin-induced membrane depolarization. The magnitude of depolarization caused by gastrin was unchanged on removal of medium Na+. Furosemide but not tetraethylammonium inhibited the gastrin-induced depolarization. The results suggest that the Ca2+ released from the store(s) induces membrane depolarization, possibly via modulation of a Cl− efflux across the luminal surface during gastrin stimulation.