Recent studies have shown that about 70 to 90% of Orientals metabolize rapidly alcohol mainly because of an ADH polymorphism, but in about 50% of them there is an undue accumulation of aldehyde due to a relatively inefficient or completely inefficient variant of ALDH₂. In addition, it has been suggested that severeness of the alcohol intoxication depends to a considerable degree on the genotype of the individual having ALDH₂ deficiency. We have therefore initiated a series of experiments designed ultimately to test the hypothesis that grade of alcohol sensitivity and adverse reactions as well as alcohol drinking habits may be correlated with certain combinations of the genotypes of alcohol and aldehyde dehydrogenase. Genotyping was performed by the enzymatic amplification (PCR) of the ADH₂ and ALDH₂ genes from blood DNAs of all the probands, and the subsequent allele-specific hybridization using the primers and allele specific oligonucleotides. ALDH₂ phenotypes (alcohol sensitivity) were assessed by the ethanol patch test (EPT). Data concerning the drinking habits were collected from intensive questionnaires with all the probands. Our study from 24 individuals in five twin families showed that a) individuals carrying the mutant ALDH₂ gene in either heterozygous or homozygous form are always sensitive against alcohol, implying dominance of the mutant allele over the normal allele; and b) no correlations exist between atypical ADH and the severeness of the alcohol intoxication. Computer-assisted evaluation of the data are presently underway to analyze a possible relationship between the frequency of ADH/ALDH₂ phenotypes and genotypes, alcohol sensitivity and alcohol drinking habits.