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Abstract. This study investigated the involvement of tryptase and proteinase-activated receptor (PAR) subtypes in spontaneous scratching, an itch-associated behavior, in NC mice. This strain of mice showed chronic atopy-like dermatitis and severe spontaneous scratching, when kept a long time in a conventional environment. The trypsin-like serine proteinase inhibitor nafamostat mesilate (1 -10 mg/kg) dose-dependently inhibited spontaneous scratching in mice with dermatitis. The activity of tryptase was increased in the lesional skin, which was inhibited by nafamostat at a dose inhibiting spontaneous scratching. Enzyme histochemistry revealed the marked increase of toluidine blue-stained cells, probably mast cells, with tryptase activity in the dermis of the lesional skin. Intravenous injection of anti-PAR 2 antibody suppressed spontaneous scratching of mice with dermatitis. Intradermal injection of the PAR 2 -activating peptide SLI-GRL-NH 2 , but not PAR 1 , 3 , 4 -activating peptides, elicited scratching at doses of 10 -100 nmol/site in healthy mice. PAR 2 -immunoreactivity was observed in the epidermal keratinocytes in healthy and dermatitis mice. These results suggest that PAR 2 and serine proteinase(s), mainly tryptase, are involved in the itch of chronic dermatitis.