To examine the possible involvement of the alpha-1-antichymotrypsin gene (ACT) polymorphism in the manifestation of Alzheimer's disease (AD), we analyzed genotypes of the ACT and apolipoprotein E gene (APOE) among 110 Korean patients with probable AD and 209 nondemented controls. No significant difference was obtained in genotypic (chi(2)=1.98, df=2, P>0.1) and allelic frequencies (chi(2)=1.61, df=1, P>0.1) of ACT between the AD and control groups. No overexpression of the ACT A/A genotype and ACT A allele was found when we analyzed the late-onset AD patients and the early-onset AD patients, separately. Then we stratified the ACT genotypes based on the presence or absence of the APOE epsilon4 allele to evaluate the possible interaction between them. In the APOE epsilon4-negative subjects, although the ACT A allele tended to be overexpressed in the AD group, the differences in the frequencies of the ACT A allele (chi(2)=2.79, df=1, P>0.1) and ACT A/A genotype (chi(2)=0.16, df=1, P>0.1) were not statistically significant. No significant overrepresentations of the ACT A allele (chi(2)=0.02, df=1, P>0.1) and ACT A/A genotype (chi(2)=0.17, df=1, P>0.1) were found in the APOE epsilon4-positive subjects, either. In addition, the status of the ACT genotype did not influence the age-at-onset of AD (F=0.03, df=2, P>0.1). Therefore, the ACT polymorphism does not contribute to the development of AD independently or interactively with the APOE epsilon4 allele in Koreans.