The genotypes of the CYP2E1 loci of 35 alcoholic and 130 nonalcoholic (healthy controls) Japanese were investigated to determine the relationship between CYP2E1 (C/D) polymorphism and susceptibility to alcohol dependence. There was a significant (d.f. = 1, chi2 = 11.0, p < 0.001) difference in the CYP2E1 C gene frequency between alcohol dependents (0.41) and controls (0.28), suggesting that the C gene of CYP2E1 may be related to the risk of developing alcoholism in Japanese, whereas the frequency of the D gene was higher among controls than alcoholics. Healthy Japanese controls showed a significantly (d.f. = 1, chi2 = 30.1, p < 0.001) higher frequency of the C allele than Swedish healthy controls (0. 10) did.