Utilizing digital imaging microscopy, the receptor-mediated changes in cytosolic Ca 2 + concentration ([Ca 2 + ] i ) were studied in fura-2-loaded rat parotid acinar cells. The increase in [Ca 2 + ] i induced by carbachol was initiated in the apical pole of the acinar cells and then spread as a Ca 2 + wave toward the basolateral region. A similar polarization of Ca 2 + signal was observed when the acinar cells were stimulated with substance P or phenylephrine. As the microsomal Ca 2 + -ATPase inhibitor thapsigargin did not produce a Ca 2 + wave, activation of phosphoinositide hydrolysis is probably essential to trigger the Ca 2 + wave. Stimulation with 1 μM isoproterenol, a concentration which causes the maximum release of amylase, had no effect on [Ca 2 + ] i . Extracellular ATP (0.5 mM) induced a homogeneous increase in [Ca 2 + ] i throughout the cells in the presence of extracellular Ca 2 + but did not change [Ca 2 + ] i in the absence of extracellular Ca 2 + , indicating that the ATP-induced rise in [Ca 2 + ] i is due to Ca 2 + entry.