Alzheimer's disease (AD) is a complex multi-factorial disease with the involvement of several possible genes. The apolipoprotein E*4 (APOE*4) allele of the known susceptibility gene, APOE, is neither necessary nor sufficient to cause AD. This has prompted the search for other candidate genes associated with the risk of AD. Cathepsin D (Cat D) is an intracellular aspartyl protease that has been reported to have in vitro beta and gamma-secretase activity. The presence of a C-->T (Ala-->Val) polymorphism in exon 2 of the Cat D gene has been reported to be associated with an increased risk of AD. Further, as inflammation is reported to play a prominent role is AD pathogenesis, IL-6, a known mediator of inflammation, is another candidate gene proposed to be associated with the risk of AD. Genetic variation in the IL-6 gene has been reported to be associated with the risk of AD. We performed a genetic screening of sporadic, late-onset AD cases and age-matched controls to evaluate the role of Cat D and IL-6 polymorphisms in AD. Our data indicate no significant association between these polymorphisms and the risk of AD. When the data were stratified by APOE*4 status, no significant difference was seen either between cases and controls. These data suggest that the Cat D and IL-6 polymorphisms do not significantly alter the risk of AD in our case-control cohort.