The present study was performed to develop a new chronic itch model accompanied by skin lesions using hairless mice. The effects of some drugs on the itch response in this model were also studied. 2,4,6-Trinitrochlorobenzene (TNCB) was applied repeatedly on the rostral back of sensitized hairless mice every 2 days for 54 days, and the scratching behavior was observed on day 0, 18, 36 and 54. The skin symptoms and total IgE level were also observed. The number of scratches observed at 24 and 48 h after TNCB challenge was increased gradually from day 18 to day 54. An intimate relationship was observed between the number of scratches and the skin score at 48 h after TNCB on day 54. The skin symptoms and total IgE levels were also elevated gradually from day 18 to day 54. Chlorpheniramine, cyproheptadine and methysergide caused no effect on the scratching behavior accompanied by skin lesions at 48 h after TNCB challenge, even at a high dose. On the other hand, L-733,060, naloxone, naltrexone, prednisolone and dexamethasone caused a significant inhibition of the scratching behavior induced by TNCB. Therefore, this model may be useful to evaluate the effects of drugs on the itch response accompanied by skin lesions, such as atopic dermatitis.