Individual pancreatic beta-cells were used to study the glucose effects on the handling of Ca2+, Sr(2+)and Ba2+. In extracellular medium containing one of these ions, single beta-cells responded to 11 mM glucose with large amplitude oscillations in cytoplasmic Ca2+, Sr2+ or Ba2+ with indistinguishable average frequencies (0.30-0.33/min). The oscillations disappeared after hyperpolarization with 400 mu M diazoxide. Under such hyperpolarization, glucose stimulated the sequestration of Ca2+ and Sr2+ but not of Ba2+ in the inositol 1,4,5-trisphosphate sensitive pool repetitively mobilized by consecutive exposures to 100 mu M carbachol. A 2-3 min exposure to 100 nM of the intracellular Ca2+-ATPase inhibitor thapsigargin also mobilized Ca2+ and Sr2+ and irreversibly abolished subsequent release by carbachol. However, thapsigargin did not prevent the large amplitude oscillations in Ca2+, Sr2+ or Ba2+ under non-hyperpolarizing conditions although the frequency of the Ca2+ oscillations was almost doubled, The results indicate that the slow oscillatory behavior of glucose-stimulated individual beta-cells does not depend on inositol 1,4,5-trisphosphate mediated release of intracellular Ca2+.