Brain tissue of 50 patients with morphological confirmed Parkinson's disease (PD), blood samples from 149 patients with clinical parkinsonism and from 96 healthy control subjects were collected. Apolipoprotein-E (apo E) and cytochrome P450 2D6 (CYP2D6) genotyping were performed by PCR followed by restriction fragment analysis. A significantly higher allele frequency of CYP2D6*4 was found in patients with PD (35%) but not with parkinsonism (14.1%) compared to control subjects (19.8%). The combined alleles frequency of CYP2D6*3 + apoE4 was significantly higher not only in the PD group (33.3%) but also in patients with parkinsonism (22.3%) compared to control subjects (1.6%). These results suggest that there is a substantial overlap not only in the clinical manifestation but also in the genetic risk factors between Parkinson's and Alzheimer's diseases.