This study was designed to investigate the hypothesis that deletion/insertion (D/I) polymorphism of the angiotensin-converting enzyme (ACE) gene may contribute to increased risk of Parkinson's disease (PD). A case-control study was carried out to examine the association between the ACE genotype and the allele frequency in 127 sporadic PD patients compared with 198 healthy controls. The frequency of the homozygote DD genotype of the ACE gene was significantly increased in patients with PD than in the controls (chi(2)=6.09, p=0.048), despite that there was no significant difference in D/I allele frequency (chi(2)=2.25, p=0.133). Moreover, PD patients carrying the homozygote DD genotype were 1.13 times more frequent than subjects without the DD genotype (chi(2)=5.67, 95% CI=1.01-1.25, p=0.017). A stepwise logistic regression analysis of the presence of the DD genotype and data on risk factors for PD confirmed that the homozygote DD genotype was a modest independent risk factor for PD (OR=1.32, 95% CI=1.12-2.16). In addition, there was a trend of increasing number of DD genotype in older PD patients and the modest risk factor of DD genotype in PD was due to the significant difference of the DD homozygosity in old patients with onset age at or after 60 years. In conclusion, results of our study support the hypothesis that the ACE gene may indicate genetic susceptibility to PD, particularly in older individuals.