Itch, a skin sensation that provokes a desire to scratch, is a common complaint. Severe itch accompanying various skin diseases such as atopic dermatitis is an important issue related to the quality of life. Although histamine from mast cells has been thought to play an essential role in itch, many severe pruritic diseases respond poorly to the H(1) histamine receptor antagonists. Therefore the precise mechanisms and mediators of itch in most pruritic diseases are unclear. To investigate the detailed mechanisms of the induction of itch, we have developed a mouse model. Studies using this model have demonstrated that keratinocytes play an important role in the induction of itch. The identification of keratinocyte stimulus factors and of products in keratinocytes could lead to developing new antipruritic medicines.