We compared the distribution of an insertion (I)/deletion (D) polymorphism of the gene coding for the angiotensin-converting enzyme (ACE) in 133 Japanese sporadic Alzheimer disease (AD) patients with 257 controls. The association between AD and ACE genotypes or alleles was found to be significant. The frequency of II genotypes was 1.4 times higher in AD than controls, while that of DD genotypes was only 0.4 times as high. The altered distribution of ACE alleles in patients with AD appeared to be independent of apolipoprotein E.