We investigated genetic polymorphism of the cytochrome P-450 CYP2D6 gene from white patients with idiopathic Parkinson's disease (IPD). The mutations of the CYP2D6 gene associated with the poor metabolizer (PM) phenotype of the debrisoquine/sparteine polymorphism were analyzed in DNA of 130 IPD patients by a polymerase chain reaction (PCR)-based DNA amplification combined with Xba I restriction fragment length polymorphism (RFLP) analysis in 105 patients. Another mutation located in exon 6 was analyzed by Hha I RFLP in 94 IPD patients. The frequencies of the different CYP2D6 gene mutations were compared to the frequencies in sex- and age-matched white control population with chronic bronchitis. The rate of genotypically defined PM and the frequencies of the different mutations were not significantly different in IPD patients and controls. These results fail to confirm the previously reported results concerning CYP2D6 gene mutations in IPD. These equivocal results might be related to methodologic problems. However, other hypotheses have been suggested: impairment of neuronal CYP 2D6 expression, transient modification of CYP 2D6 phenotype, or linkage of CYP2D6 gene to the candidate gene locus directly involved in IPD.