Mast cell granules, obtained from sonically disintegrated rat peritioneal cells and suspended in sucrose, 0.34 M, were found to release histamine in the presence of bee venom. Three venom fractions were obtained by gel filtration; two of these had strong histamine releasing capacity, namely “F I” containing phosphatidase A, and “F III” with direct hemolytic properties. The third fraction, “F II”, which releases histamine from intact mast cells, had little effect on granules. Various possibilities for the release mechanism, namely phosphatidase activity, surface activity, and cation exchange, are discussed.