Background: Interleukin-6 (IL-6) is an inflammatory cytokine with increased activity in the brain of patients with Alzheimer's disease (AD), leading to accumulation of acute phase proteins (e.g., α1-antichymotrypsin, ACT) in neuritic plaques. Genetic polymorphisms of the IL-6 gene are associated with increased activity of IL-6 in vivo. We tested the hypothesis, whether these variations of the IL-6 gene are associated with AD and whether they interact with other potential risk factors for AD (i.e., apolipoprotein E [ApoE] and ACT polymorphisms). Method: The investigation was carried out on specimens from a regional family study on AD and geriatric depression. Blood samples were drawn from 107 AD patients and 102 age- and sex-matched healthy controls. A variable number tandem repeat (VNTR) polymorphism situated in the AT-rich 3′ flank of the IL-6 gene was studied by using genomic DNA and PCR amplification. Amplification products were separated by 4% agarose gel electrophoresis and visualized by GelStar® staining. Differences in the allelic distribution between groups were tested by the χ2-test. Results and Conclusions: Genotypic analysis showed evidence of six length variants of the IL-6 gene (alleles A-F) ranging between 640 and 830 bp. The majority of study participants fell into the categories F/F and C/F. B/F and E/F genotypes were rare in the present sample. Analysis of interactions between IL-6 and ACT polymorphisms might be important to understand the role of the genetically determined immune response in the pathogenesis of AD. However, larger samples are required as the relevant genotypic combinations are rare.