Idiopathic Parkinson's disease (PD) is a multifactorial neuro-degenerative disorder resulting from environmental factors acting on genetically susceptible individuals with normal aging. Cytochrome P450IA1 is a dioxin-inducible enzyme which is responsible for the activation of procarcinogens and environmental pollutants, such as benzo[alpha]pyrene and other aromatic hydrocarbons. The frequencies of polymorphic alleles of cytochrome P450IA1 gene (CYPIA1) were studied in 126 unrelated patients with PD in comparison with 176 healthy Japanese. The frequency of the Msp I polymorphic allele, a variant of CYPIA1 (m2), was significantly higher in patients with PD (0.444) than in controls (0.349). The risk of PD in homozygotes for m2 was 2.34-fold greater than homozygotes for the wild-type, m1. The relative risk for PD in homozygotes for CYPIA1Val was 6.54-fold higher than in homozygotes for the wild type (CYPIA1Ile)(p < 0.001). These results strongly suggest that the CYPIA1 might be one of the susceptibility genes for PD.