To clarify the mechanism of secretagogue (compound 40/80)-induced calcium signaling in rat peritoneal mast cells, we analyzed serial confocal calcium images with high spatial and temporal resolution using different Ca2+-probes. The Ca2+-wave began at the periphery of the cytoplasm, and then spread to the center of the nucleus. Nuclear [Ca2+]i was clearly higher than cytoplasmic [Ca2+]i. The heterogeneity of [Ca2+]i continued until about 2 min after degranulation. These results suggest the existence of an intranuclear Ca2+-store which possesses a Ca2+ -releasing mechanism similar to that in the cytoplasm.