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Analgesic effect of Keishi-Ni-Eppi-Itto-ka-Ryo-Jutsu-Bu (KNE), a traditional herbal medicine against rheumatoid arthritis, on writhing reaction induced by acetic acid was investigated in mice. KNE, composed of gypsum, Zizyphi fructus, Cinnamomum cortex, Ephedrae herba, Paeoniae radix, Glycyrrhiza, ginger, Atractylodis rhizoma and hoelen, significantly depressed the writhing reaction, while Aconiti tuber, widely used for analgesic purpose, did not affect the reaction. The depressive action of each KNE component was examined. It was found that only Ephedrae herba showed significant dose-dependent depression of the writhing reaction. When the decocted liquid of Ephedrae herba was separated to aqueous layer and benzene layer at low pH, followed by high pH, the aqueous layer showed remarkable dose-dependent depression of the writhing reaction.