It has been reported that acetaldehyde may be a main factor of alcohol-induced bronchoconstriction in Japanese patients with asthma. The purpose of this study was to investigate the direct action of acetaldehyde on the airway in asthmatic and healthy nonasthmatic subjects. We investigated the bronchial response to inhalation of ascending doses (5, 10, 20, and 40 mg/ml) of acetaldehyde in nine asthmatic subjects, who were treated with placebo or terfenadine for 4 days in a double-blind, randomized, placebo-controlled, crossover fashion, and in nine age- and sex-matched healthy subjects. The bronchial responsiveness to inhaled methacholine was also measured in the same asthmatics on a separate day. Inhaled acetaldehyde caused marked (more than 20%) significant decrease in FEV1 in asthmatics after placebo, which was larger than that in asthmatics after terfenadine and in healthy subjects. There was no significant difference in the decrease in FEV1 between asthmatics treated with terfenadine and healthy subjects. There was a significant correlation between the methacholine and acetaldehyde concentrations producing a 20% fall in FEV1 in asthmatics. We conclude that acetaldehyde causes bronchoconstriction indirectly via histamine release in asthmatics, and that nonspecific bronchial hyperresponsiveness is a necessary precondition for the expression of acetaldehyde-produced bronchoconstriction.