beta 2-Microglobulin (B2-MG) content was measured for the first time in the brain (caudate nucleus, putamen, and cerebral cortex) from control and parkinsonian patients by a highly sensitive sandwich enzyme immunoassay. The concentrations of B2-MG in dopaminergic striatal regions were significantly higher in parkinsonian patients than those in controls, whereas those in the cerebral cortex showed no significant difference between parkinsonian and control subjects. Tumor necrosis factor-alpha (TNF-alpha) concentrations were also increased in the striatum, confirming our previous findings, but not in the cerebral cortex. Since TNF-alpha may induce B2-MG expression, these results suggest that an immunological response may occur in the nigrostriatal dopaminergic regions in Parkinson's disease.