We tested 100 schizophrenics and 100 controls to find association at the Serine311 Cysteine polymorphism of dopamine D2 receptor in Japanese population. There were no significant differences between the two groups. One homozygote for Cys311 was confirmed in the controls by mismatch-polymerase chain reaction and restriction fragment length of polymorphism (PCR-RFLP) analysis. None with Cys was detected among 61 individuals of nine multiply affected families with schizophrenia. Our data thus provide strong evidence against an etiological association between schizophrenia and the Ser311Cys variant. The polymerase chain reaction amplification of specific alleles (PASA) analysis was compared with the mismatch PCR-RFLP typing, revealing that the latter is more reliable than the former.