We have examined a variant of the dopamine D2 receptor gene (Ser311-->Cys) in 156 Japanese schizophrenic patients and 300 controls. The allele frequency of Cys311 was significantly higher in the whole patient group (0.054), among patients with onset before age 25 (0.090), and among those with a family history (0.135) than in the controls (0.018). 3 patients were homozygous for Cys311. The patients with Cys311 showed significantly less severe thought disorder and negative symptoms of schizophrenia than those without Cys311. The Cys311 variant of the D2 receptor may be a genetic risk factor for some types of schizophrenia.