Clinical and immunopathological evidence support a potential role of the pro- and anti-inflammatory cytokine network in neurodegeneration of Alzheimer's disease (AD). Moreover, association studies suggest a possible involvement of cytokine-related genes in the susceptibility to sporadic AD. Since conflicting results are associated with the pro-inflammatory pathway, we investigated a putative effect of the anti-inflammatory counterpart focusing on the interleukin-10 (IL-10) gene. The 5' flanking region contains numerous polymorphisms; in particular, three single nucleotide polymorphisms (-1082 G/A, -819 T/C, -592 C/A) are in linkage disequilibrium resulting in three haplotypes GCC, ACC and ATA. We analyzed the IL-10 haplotype distributions in 215 Italian sporadic AD patients and 153 controls in an association case-control study. Haplotype frequencies did not reveal differences between the two samples, however the genotype GCC/ACC was more represented in AD patients (OR 1.91, 95% CI: 1.18-3.07). This putative risk factor could be independent of the presence of the ApoE epsilon 4 allele. Our results provide new insights on a possible involvement of the IL-10 gene in susceptibility to sporadic AD even though further functional and genetic investigations are necessary to clarify its role in AD.