Tritoqualine (TRQ), used clinically as an antiallergic drug, did not inhibit histidine decarboxylase activity (HDC, EC. 126.96.36.199.) partially purified from fetal rats and the enzymes prepared from mastocytoma P-815 cells. However, TRQ inhibited the histamine release from rat peritoneal mast cells induced by compound 48/80 and ATP. TRQ was also effective in inhibiting antigen-induced histamine release in rat mast cells sensitized actively or passively by the homologous anti-DNP-Ascaris antibody. Preincubation of cultured mastocytoma P-815 cells in a medium including TRQ inhibited non-cytotoxically the histamine release of mastocytoma cells induced by compound 48/80, and the effect of TRQ became more marked with lengthening of the culture period in the presence of TRQ. It was concluded from these results that one of the main actions of TRQ as an antiallergic drug was not the inhibitory action on HDC, but might be ascribed to its inhibitory effect on histamine release from mast cells.