The effect of tranilast, an inhibitor for IgE-mediated mediator release from mast cells, on plasma extravasation induced by the intradermal injection of substance P in rats was examined. Tranilast (100 mg/kg, intraperitoneally) decreased plasma extravasation induced by substance P (10(-7)-10(-5) M). Tranilast decreased plasma extravasation induced by the amino-terminal peptide substance P1-9 (10(-6)-10(-4) M), which is active for rat mast cells, but not by the carboxy-terminal peptide substance P6-11 (10(-6)-10(-4) M), which is inactive for the mast cells. Therefore, tranilast prevents substance P-induced plasma extravasation most likely by inhibiting mast cell degranulation.