α-Synuclein is mutated in some hereditary cases of Parkinson's disease and the protein precipitates in Lewy bodies, the pathological hallmark of both Parkinson's disease and Lewy body disease. Transgenic mice overexpressing human wild-type α-synuclein develop α-synuclein-immunoreactive inclusions in brain regions typically affected with Lewy body disease. We used in situ hybridization to characterize α-synuclein expression and examine mRNA levels in patients affected with Lewy body disease and controls. Substantia nigra was avoided because of the extensive neuronal loss and cingulate gyrus was chosen as it is one of the diagnostic regions in Lewy body disease where Lewy bodies most frequently are demonstrated. β-tubulin was used to control for neuronal degeneration. The α-synuclein probe showed intense labeling of pyramidal cells in lamina III and V in both patients and controls. We found no difference in α-synuclein mRNA levels and β-tubulin mRNA was not significantly altered (P=0.06) in patient brains. There was no difference in the ratio of α-synuclein and β-tubulin mRNA levels between patients and controls. Further, we found no relationship between α-synuclein mRNA levels and Lewy bodies. Great variability in α-synuclein mRNA levels among patients indicates that Lewy body disease may be a heterogeneous disorder with regard to α-synuclein involvement. © 2001 Elsevier Science B.V. All rights reserved.