Recently ethanol-induced bronchoconstriction associated with elevated serum levels of acetaldehyde and histamine was reported in Japanese asthmatic patients, but there is no investigation of the airway response to intravenous injection of acetaldehyde. We therefore performed a study in guinea pigs to test the hypothesis that intravenous injection of acetaldehyde has bronchospastic action via histamine release. At first, we investigated the airway response to increasing doses (8.0, 26.4, and 80 mg/ml) of injected ethanol or acetaldehyde in guinea pigs. Secondarily, increasing doses of acetaldehyde were injected in guinea pigs pretreated with an intraperitoneal injection of 20 mg/kg diphenhydramine or saline (control). Finally, injection of acetaldehyde was performed after intraperitoneal injection of 0.5 mg/kg atropine sulfate or saline (control). Injected acetaldehyde caused bronchoconstriction in a dose-dependent manner, but ethanol did not. The bronchoconstriction induced by injected acetaldehyde was completely prevented by pretreatment with diphenhydramine. Atropine had no preventing effect against the acetaldehyde-induced bronchoconstriction. In conclusion, intravenous injection of acetaldehyde causes bronchoconstriction via histamine release in guinea pigs.