To examine the relation between the microsatellite polymorphism of alpha 1-antichymotrypsin (AACT) gene and Alzheimer's disease (AD) in Han population of Shanghai area, and to detect the influences of apolipoprotein E (ApoE) gene epsilon 4 allele on this relation.The polymorphism of AACT and ApoE gene were genotyped in 63 AD cases, 62 controls with amplified fragment length polymorphism typing (Amp-FLP).The frequencies of A6 and A10 alleles of the microsatellite polymorphism of AACT gene polymorphism were decreased markedly (ZA6 = 2.2357, ZA10 = 1.9668, P < 0.05), but only A6 allele was negatively associated with AD (RR = 0.4, chi 2 = 4.683, P < 0.05). When the data were split into ApoE * epsilon 4-positive and ApoE * epsilon 4-negative groups, the drop of AACT * A6 allele frequency was only associated with AD with non-ApoE epsilon 4 (RR = 0.29, chi 2 = 3.197, P < 0.05).AACT * A6 allele may be associated with AD negatively in Shanghai area, and this effect only exists in non-ApoE * epsilon 4 AD.