There exists considerable evidence implicating abnormalities of the alpha (alpha)-adrenergic system in the development of Alzheimer disease (AD). We propose to investigate potential correlations between the presence or otherwise of alpha-adrenoceptor polymorphisms and the presence of AD. We studied the polymorphisms of the alpha1a- and the alpha2a-adrenoceptor genes in 142 AD patients and 98 normal controls. The result demonstrated that none of the alpha2a-adrenoceptor genotypes was associated with increased susceptibility to AD. However, there was a trend that the frequency of the C allele of the alpha1a-adrenoceptor was elevated and an excess of the CC genotype (90.1%) was found in the subjects with AD in comparison with the controls (78.6%). This association was unrelated to the apolipoprotein E genotypes. The hypothesis that the alpha1a-adrenoceptor gene may be implicated in the pathogenesis of AD may deserve further study.