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ABSTRACT: The present study was performed to study the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on scratching behavior in hairless mice, which are highly sensitive to pruritogens (mediators causing itching), except for histamine, and are suitable for time-course studies due to their hairless skin. TCDD is a well-known environmental pollutant that causes skin diseases with itching; therefore, we examined whether TCDD induced itching. Oral administration of TCDD caused no increase in scratching behavior when used alone, whereas TCDD in combination with distilled water or acetone/olive oil application caused a significant increase in scratching behavior. Furthermore, nerve growth factor (NGF) content in the skin increased significantly. A single administration of chlorpheniramine (histamine H1 receptor antagonist), tranilast (chemical mediator release inhibitor) and olopatadine (histamine H1 receptor antagonist) had no effect on scratching behavior induced by TCDD in combination with acetone/olive oil application. With repeated administration for 7 days, chlorpheniramine and tranilast had no effect on scratching behavior, whereas olopatadine significantly inhibited scratching behavior. In addition, only olopatadine significantly inhibited NGF content in the skin. From these findings, it can be concluded that TCDD is not a pruritogen but causes alloknesis (itchy skin) with the simultaneous use of trivial external stimulation. In addition, it was found that drugs which decreased skin NGF contents may inhibit this scratching behavior.