Mutations in the alpha-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) genes have been linked to some cases of familial Parkinson's disease. To provide insight into how these genes may relate to each other and contribute to the pathology of Parkinson's disease, their expression was examined in normal human brain. Tissue sections from multiple regions of 11 normal human brains were hybridized with radiolabeled and digoxygenin-labeled cRNA probes for alpha-synuclein, parkin, and UCH-L1 mRNA. Expression of each of these three genes was predominantly neuronal. Alpha-synuclein and parkin mRNAs were expressed in a restricted number of brain regions, whereas UCH-L1 mRNA was more uniformly expressed throughout brain. The melanin-containing dopamine neurons of the substantia nigra had particularly robust expression. The expression patterns of alpha-synuclein and parkin mRNAs were similar, suggesting that these two proteins may be involved in common pathways contributing to the pathophysiology of Parkinson's disease.