Genotypes of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) loci were determined, using allele specific oligonucleotides. Gene frequencies of ADH2(1) and ADH2(2) were 0.29 and 0.71, respectively, in the Japanese control group. No significant difference was found in the ADH2 genotype between the patients and the control group. Gene frequency of ALDH2(1) and ALDH2(2) were 0.65 and 0.35 in the control group, while 0.93 and 0.07, respectively in the patient group. Most of the patients, 20 out of 23, were homozygous Caucasian type. All individuals with homozygous atypical ALDH2(2)/ALDH2(2) and most of those with heterozygous atypical ALDH2(1)/ALDH2(1) were alcohol flushers, while all of the usual ALDH2(1)/ALDH2(1) were nonflushers. The results indicate that Japanese with the atypical ALDH2(2) allele are at a much lower risk in developing alcoholic liver disease than those with usual ALDH2(1)/ALDH2(1), presumably due to their sensitivity to alcohol intoxication.