Clinical observations indicate that a proportion of patients with schizophrenia experience cognitive impairment, which suggests that a neurodegenerative basis might be involved in the etiology of schizophrenia. Apolipoprotein E (ApoE), which has been confirmed to be genetically associated with Alzheimer's disease, is thus highlighted as a candidate gene for schizophrenia. Recently, novel functional polymorphisms in the ApoE transcriptional regulatory region have been found. To investigate whether these polymorphisms are associated with the risk of schizophrenia, we genotyped 144 patients with schizophrenia and 134 controls for two polymorphisms (-491A/T and -219G/T). No significant positive associations between both polymorphisms and schizophrenia were observed. Our findings exclude the regulatory region of the ApoE gene as a locus that might confer increased susceptibility to schizophrenia.