SummaryWe investigated genetic polymorphism of the cytochrome P450 CYP 2D6 gene in 105 Caucasian patients with idiopathic Parkinson's disease (IPD) and 15 patients with diffuse Lewy body disease (DLBD). The mutations of the CYP 2D6 gene associated with the poor metabolizer (PM) phenotype of the debrisoquine/sparteine polymorphism were analyzed in DNA by a polymerase chain reaction (PCR)-based DNA amplification combined with Xba I restriction fragment length polymorphism (RFLP) analysis. The rate of genotypically defined PM and the frequencies of the mutation D6-B were not significantly different in IPD and DLBD patients. This study fails to find a relationship between CYP 2D6 impairment and neuropathological lesions diffusion in IPD and DLBD. This study cannot exclude involvement of neuronal expression of CYP 2D6.