We studied promoter region polymorphisms in the tumor necrosis factor (TNF) gene at position -1031, -863, and -857, in 172 Japanese patients with sporadic Parkinson's disease (PD). The frequency of the -1031C allele, a high producer of TNF, increased significantly in early onset PD patients compared with controls. In addition, PD patients with the -1031C allele showed a significantly earlier onset than those without -1031C allele, after stratification of the data by an interleukin-1beta gene polymorphism. Our findings suggest that TNF might have a toxic effect in PD.