Excessive alcohol consumption is a potent risk factor for high blood pressure. About half of Japanese show an extremely high sensitivity to alcohol, which is due to a genetic deficiency in an isoenzyme of aldehydede-hydrogenase with a low Km (ALDH2). It is possible that the effects of alcohol consumption on blood pressure differ according to the ALDH2 genotype. The purpose of the present study was to assess the influence of the ALDH2 genotype on the pressor effects of alcohol. The influence of the ALDH2 genotype on blood pressure was investigated in a large cohort (4,000 subjects) representing the general population in Japan. The genotype was determined by the TaqMan method. The genotype was significantly associated with alcohol consumption, gamma-GTP level, and HDL cholesterol level in both males and females. The odds ratio for the presence of hypertension for the Glu/Glu genotype in comparison to other genotypes was 1.67 (p< 0.0001, odds ratio=1.37-2.08, 95% confidence interval) among males. In contrast, the ALDH2 genotype had no significant effects on blood pressure among females. To investigate whether the ALDH2 genotype affected the sensitivity to the pressor effects of alcohol, we analyzed the effects of the ALDH2 genotype (Lys/Lys+Lys/Glu=0, Glu/Glu=1) and the level of alcohol consumption on blood pressure values after adjusting for age and BMI (residuals after adjusting for age and BMI). Among males, while the level of alcohol consumption significantly affected systolic, diastolic and pulse pressure, no significant interaction was observed between the ALDH2 genotype and the level of alcohol consumption in determining blood pressure levels. These results suggest that the Glu/Glu genotype is a potent risk factor for hypertension among males mainly through its association with the level of alcohol consumption, and that the ALDH2 genotype does not affect the sensitivity to the pressor effects of alcohol.