Linkage studies have suggested that chromosome 15q13-q14 may harbor a susceptibility locus for schizophrenia. In the current study, the association between a (AC)n dinucleotide repeat polymorphism at D15S118 and schizophrenia was investigated using three independent samples from the Han Chinese population and the Scotland population. In the population-based study, a significant difference was found between the allele frequency distributions in schizophrenia patients and control subjects in the Scottish samples (P = 0.04), but was not replicated in the Chinese samples. In a family-based study, no significant transmission disequilibrium from heterozygous parents to affected offspring was observed. Overall, our results did not support the hypothesis that the (AC)n dinucleotide repeat polymorphism plays a major role in schizophrenia susceptibility, at least in the Chinese population. Further studies are needed to elucidate its role in schizophrenia susceptibility in European population.