Most of the histamine in mast cells is known to be stored in specific granules (1-3), but as for the mode by which histamine is bound within the granules, opinions are not in harmony. Thus, a hypothesis has been proposed that histamine is bound electrostatically to anionic sites of the heparin-protein complex of the granule constituents from which histamine is easily released by ionic exchange when the isolated granules are exposed to cations in the medium (4-7). However, many classical experiments have indicated that histamine in mast cell granules is not so susceptible to the releasing action of inorganic cations of the outer milieus (8-12). A possible reason for the discrepancy may be changes in the properties of mast cell granules during the isolation procedures. In the present paper, this assumption has been supported by the observation that there are considerable differences in the histamine release by inorganic cations from mast cell granules depending on the method of granule isolation.