Abstract.Gastric parietal cells in primary culture have been tested to determine their utility as a model for the study of the role of intracellular calcium ([Ca2+]i) in the control of HCl secretion. Changes in [Ca2+]iwere measured in single cells on a microscope stage using the cell‐permeant form of the fluorescent calcium probe, fura‐2. Simultaneous images of cell fluorescence and morphology were acquired using a digitized video image analysis system and two video cameras, one for low‐light level fluorescence detection and one for high resolution DIC/transmitted light images. Both histamine and carbachol, which are known stimulants of HCl secretion, increased [Ca2+]iand stimulated dramatic changes in morphology in these cultured cells. Changes in morphology were accompanied by an increased uptake of the weak base, [14C]‐aminopyrine (AP), and a shift from green to red fluorescence of another weak base, acridine orange. These results indicate that cultured parietal cells, maintained under controlled conditions on a microscope stage, retain viability and secretagogue responsiveness. Thus, this cellular model appears to be suitable for correlation of changes in [Ca2+]iand activation of HCl se