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To investigate the relation between extracellular Ca2+ and histamine release, we observed agonist-induced his-tamine release from RBL 2H3 mast cells in the presence or absence of extracellular Ca2+ concentration. Histamine releaseinduced by melittin and thapsigargin were greater in the presence of extracellular Ca2+ than in the absence of extracellularCa2+ . Econazole-induced histamine release had nothing to do with extracellular Ca2+ , whereas arachidonic acid-induced his-2+ . Calmodulin antagonists did not affect melittin-induced his-tamine release but they may potentiate arachidonic acid-induced histamine release. These data suggest that arachidonicacid-induced histamine release may be mediated via Ca2+ -independent pathway and may be potentiated by the block ofCa2+ -dependent pathway.Keywords . mast cells, histamine, calcium, calmodulin antagonist..... ....... histamine. ... ... Ca2+