A recent observation has shown thar a common polymorphism in the alpha(1)-antichymotrypsin (ACT) gene modifies the apolipoprotein E (ApoE) epsilon 4-associated Alzheimer's disease (AD) risk identifying the combination of the ACT/AA. and ApoE epsilon 4/epsilon 4 genotypes as a potential susceptibility marker for AD, We analyzed the segregation of the ApoE and ACT polymorphism in sporadic and familial AD patients. in none of the sporadic AD patients did we find the combination of the ACT/AA, and ApoE epsilon 4/epsilon 4 genotypes. The frequency of ApoE epsilon 4/epsilon 4 homozygosity in the AD sample resulted highest far the ACT/TT genotype (17.6%). Our data fail to confirm any additional association with AD beyond the ApoE epsilon 4 allele with any ACT genotype, suggesting that ACT does not represent an additional risk factor for AD.