Fluorescent Ca 2+ probes and digital photo-sectioning techniques were used to directly study the dynamics of Ca 2+ in isolated mast cell granules of normal (CB/J) and beige (Bg j/Bg j) mice. The resting intraluminal free Ca 2+ concentration ([Ca 2+] L) is 25 ± 4.2 μM (mean ± SD, n = 68). Exposure to 3 μM inositol 1,4,5-trisphosphate (InsP 3) induced periodic oscillations of luminal Ca 2+ ([Ca 2+] L) of ∼10 μM amplitude and a period around 8–10 s. The [Ca 2+] L oscillations were accompanied by a corresponding oscillatory release of [Ca 2+] L to the extraluminal space. Control experiments using ruthenium red (2 μM) and thapsigargin (100 nM) ruled out artifacts derived from the eventual presence of mitochondria or endoplasmic reticulum in the isolated granule preparation. Oscillations of [Ca 2+] L and Ca 2+ release result from a Ca 2+/K + exchange process whereby bound Ca is displaced from the heparin polyanionic matrix by inflow of K + into the granular lumen via an apamin-sensitive Ca 2+-sensitive K + channel (ASK Ca), whereas Ca 2+ release takes place via an InsP 3-receptor-Ca 2+ (InsP 3-R) channel. These results are consistent with previous observations of [Ca 2+] L oscillations and release in/from the endoplasmic reticulum and mucin granules, and suggest that a highly conserved common mechanism might be responsible for [Ca 2+] L oscillations and quantal periodic Ca 2+ release in/from intracellular Ca 2+ storage compartments.