A recent observation has shown that a common polymorphism (-491 A) in the promoter of apolipoprotein E (APOE) was associated with an increased risk for Alzheimer's disease (AD) in European decent. Moreover, the promoter with -491 A showed higher transcriptional activity than that with -491 T. To investigate the further contribution of the polymorphism to the etiology of sporadic AD, we evaluated associations between Japanese AD and -491 A/T polymorphism of APOE. There was no significant difference between these cases and controls. The percentage of the homozygote of -491 A allele (AA) among the Japanese control population was significantly higher than that among the Spanish control population. The APOE promoter genotype frequencies may be influenced by the ethnic background. Our study failed to confirm any relationship between -491 A/T polymorphism and AD. Thus, we conclude that the APOE promoter polymorphism does not represent an additional risk factor for AD in Japanese populations.