Inflammatory events may contribute to the pathogenesis of Parkinson's disease (PD). We conducted a case-control study in a cohort of 369 PD cases and another cohort of 326 ethnically matched controls to investigate the association of tumor necrosis factor-α (TNF-α) promoter single nucleotide polymorphisms (SNPs) with the risk of PD. The overall genotype distribution at T-1031C and C-857T sites showed significant difference between PD cases and controls (P = 0.0062 and 0.0035, respectively). However, only the more frequent −1031 CC genotype was evidently associated with PD (P = 0.0085, odds ratio: 2.96; 95% CI: 1.38–7.09). Pairwise SNP linkage disequilibrium showed −1031 and −863 sites are in strong linkage disequilibrium (D′ = 0.93, Δ2 = 0.80). Pairwise haplotype analysis among the four sites showed that −1031C-863A may act as a risk haplotype among PD cases (P = 0.0028, odds ratio: 2.18; 95% CI: 1.33–3.69). © 2006 Wiley-Liss, Inc.