N-(3,4-Dimethoxycinnamoyl) anthranilic acid (N-5′) is an inhibitor of IgE-mediated histamine release from mast cells. To elucidate inhibition mechanism, effects of N-5′ were examined under various conditions using peritoneal exudate cells and isolated mast cells of rats. N-5′ inhibited histamine release induced by antigen, ionophore A 23187, ATP, dextran and phospholipase A2. But the release induced by compound 48/80 or ionophore X537 A was not inhibited. Influx of Ca++ into mast cells and ATP consumption were inhibited. Based on these results, it is presumed that N-5′ interferes with the energy-requiring system and/or Ca++ influx resulting in the inhibition of histamine release.