The effects of conjugated linoleic acid (CLA) against anaphylaxis and allergic pruritus were investigated using a in vivo assay. Inhibitory effects of CLA were observed on the immediate (type 1) hypersensitivity reaction, with CLA significantly suppressing the decrease in blood pressure (BP) and blood flow (BF) induced by the hen egg-white lysozyme (HEL)-anaphylactic reaction in ddY mice. After oral administration, CLA showed antipruritic activity, with significant inhibition of scratching behavior induced by compound 48/80 (COM), a histamine-release agent. When painted onto the skin, CLA also inhibited COM, platelet-activating factor, and protease-induced scratching behavior, and COM-induced vasodilation of the skin. CLA offers promise as a drug for the treatment of allergic and inflammatory pruritus not only as an oral but also a topical agent. The present findings demonstrate that CLA can be effective for the prevention and treatment of allergic disease with severe pruritus.