To examine the possible association between three recently identified structural polymorphisms of the dopamine D2 receptor (DRD2) gene and alcoholism, we compared allele frequencies of these polymorphisms in 280 Japanese alcoholics and 289 normal controls. The results revealed that only one of three variants identified in white individuals existed in the alcoholic and control Japanese. The frequency of the Cys311 variant allele was significantly higher in alcoholics (.063) than in controls (.029). All of the subjects with the variant allele were heterozygous Ser311/Cys311. Patients with Cys311 allele had less severe symptoms of alcoholism than did those with homozygous Ser311, especially symptoms related to loss of control over drinking. The coprevalence of other psychiatric disorders including schizophrenia did not differ between the two patient groups. These results suggest that the D2/Cys311 variant is associated with some type of alcoholism in Japanese.