Suplatast tosilate (suplatast) is an antiallergic agent capable of down-regulating the functions of CD4+ T cells. We now investigated the effects of suplatast on the antigen-induced airway hyperresponsiveness and the underlying allergic inflammatory response in sensitized guinea pigs. Animals that had been immunized twice by ovalbumin inhalation on day 0 and day 7 developed an increased airway responsiveness against inhaled acetylcholine 24 h after the ovalbumin challenge on day 14. Suplatast (10 and 100 mg/kg per day) and ketotifen (10 mg/kg per day) given orally from day 0 to day 14 effectively inhibited the expression of airway hyperresponsiveness. They also inhibited the infiltration of eosinophils and macrophages into broncho-bronchiolar walls and lumen. Interestingly, suplatast, but not ketotifen, inhibited the infiltration of lymphocytes including CD4+ T cells. Collectively, these results strongly suggest that suplatast prevents the expression of airway hyperresponsiveness due to the ability to suppress the infiltration of inflammatory cells into lung tissues.