The pathogenesis of Parkinson's disease may be influenced by genetic and environmental factors. Cytochrome P450 mono-oxygenases help to protect against toxic environmental compounds and individual variations in cytochrome P450 expression might, therefore, influence susceptibility to environmentally linked diseases. The frequency of mutant CYP2D6 alleles was studied in 229 patients with Parkinson's disease and 720 controls. Individuals with a metabolic defect in the cytochrome P450 CYP2D6-debrisoquine hydroxylase gene with the poor metaboliser phenotype had a 2.54-fold (95% Cl 1.51-4.28) increased risk of Parkinson's disease. Determination of CYP2D6 phenotype and genotype may help to identify those at greatest risk of Parkinson's disease and may also help to identify the environmental or metabolic agents involved in the pathogenesis of this disease.