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Effects of prostaglandin (PG) D2, PGE2, and PGI2 on itch-associated scratching responses of mice and histamine release from the rat basophilic leukemia cell line RBL-2H3 were examined. PGD2 and ketotifen but not PGE2 and PGI2 suppressed the scratching caused by ovalbumin injected into ovalbumin-sensitized mice. Ketotifen also suppressed compound 48/80-induced scratching but not PGD2, PGE2, and PGI2. In vitro, PGD2 suppressed the antigen-induced histamine release from RBL-2H3 cells, but PGE2 and PGI2 did not. These findings suggest that PGD2 specificically suppressed IgE-mediated scratching by inhibiting IgE-mediated histamine release from mast cells. Keywords:: prostaglandin D2, scratching behavior, mast cell