Abstract. Proteinase-activated receptor-2 (PAR 2 ) participates in itch, but the role of the other subtypes of this receptor remain unknown. To investigate this issue, scratching, an itch-related behavior, was observed following intradermal injections of the activating peptides of PAR 1-4 in mice. Activating peptides of PAR 1 , PAR 2 , and PAR 4 , but not PAR 3 , induced scratching. The antihistamine terfenadine suppressed scratching elicited by activating peptides of PAR 1 and PAR 4 , but not PAR 2 . These results suggest that PAR 1 , PAR 2 , and PAR 4 are involved in itch and that histamine is a cause of itch related to PAR 1 and PAR 4 , but not PAR 2 .