There is now overwhelming evidence that the varepsilon4 allele of apolipoprotein (APOE) gene is a major risk factor for late-onset Alzheimer's disease (AD). However, the APOE locus only accounts for a proportion of the overall genetic risk for AD. The angiotensin-converting enzyme (ACE) is widely expressed in the brain and may have a role in AD. Recently an insertion/deletion (I/D) DNA polymorphism at the intron 16 of ACE gene has been found associated with late-onset AD, but the results are not consistent. We have examined ACE gene in a cohort of Han Chinese AD cases and controls. We have found the ACE-I allele was enriched in our cases compared to controls (odds ratio (OR)=2.09, P=0.0043). The phenomenon was restricted to cases presenting with AD after the age of 70 years (P<0.0005), and was independent of APOE genotype. We conclude that ACE genotype is a risk factor for late onset AD.