Background: Alcohol-induced asthma, a phenomenon characteristic of Asians, is due to differences in alcohol metabolism, particularly acetaldehyde metabolism. We investigated the effect of polymorphism in acetylaldehyde dehydrogenase 2 (ALDH2) gene on the response to alcohol challenge testing in a group of Japanese asthmatic subjects and normal subjects. Methods: Subjects were 32 asthmatic subjects and 30 healthy individuals. We measured the change in FEV₁ after ingestion of 30 gm of ethanol. Blood ethanol, acetylaldehyde, and histamine concentrations were determined. ALDH2 gene type was established by polymerase chain reaction. Results: Ethanol provocation test results were positive in 15 (47% responders) asthmatic subjects. The blood ethanol concentration was similar in responders and nonresponders. The fall in FEV₁ was associated with a rise in blood acetaldehyde and histamine concentrations. The response to oral ethanol challenge was positive in three (19%) of 16 patients with normal homozygote ALDH2 genotype, 10 (71%) of 14 patients with type mutant heterozygote, and two (100%) of two patients with type mutant homozygote ALDH2 genotype. Conclusions: Alcohol-induced asthma is probably caused by increased blood acetaldehyde concentration resulting from abnormalities of ALDH2 enzyme activity based on ALDH2 genotype differences.(J Allergy Clin Immunol 1998;101:576-80).