Previous studies have demonstrated that subjects with one or twoA1alleles of dopamine D2receptor (DRD2) polymorphism at theTaq1A locus have lower DRD2density than those with noA1allele. The present study aimed to examine whether theTaq1ADRD2genotypes are related to therapeutic response to nemonapride, a selective dopamine antagonist, in schizophrenic patients. The subjects were 25 acutely exacerbated schizophrenic inpatients who had received no medication for at least 1 month before the study. The fixed dose (18 mg/day) of nemonapride was administered to each patient for 3 weeks. The clinical status was prospectively monitored by the Brief Psychiatric Rating Scale (BPRS) before, and 3 weeks after, the treatment. TheTaq1A genotypes (A1andA2alleles) were determined by the polymerase chain reaction method. Three patients were homozygous for theA1allele, 11 were heterozygous for theA1andA2alleles, and 11 were homozygous for theA2allele. The patients with one or twoA1alleles (n= 14) showed significantly higher percentage improvement in total BPRS and positive symptoms than those with noA1allele (n= 11) after 3-week treatment while the percentage improvement in other subgrouped symptoms (negative, anxiety-depression, excitement and cognitive symptoms) was similar between the two genotype groups. The present results suggest that theTaq1ADRD2polymorphism is related to early therapeutic response to nemonapride in schizophrenic patients, possibly by modifying the efficiency of DRD2antagonism of the drug in the central nervous system.