Uric acid, an antioxidant found in high concentrations in serum and in the brain, has been hypothesized to protect against oxidative damage and cell death in Parkinson's disease. The authors tested this hypothesis among men participating in a 30-year prospective study known as the Honolulu Heart Program. Serum uric acid was measured in 7,968 men at the baseline examination held from 1965 to 1968. Of these men, 92 subsequently developed idiopathic Parkinson's disease (IPD). In analyses adjusted for age and smoking, men with uric acid concentrations above the median at enrollment had a 40% reduction in IPD incidence (rate ratio (RR) = 0.6; 95% confidence interval (CI) 0.4-1.0). Reduced IPD incidence rates persisted in analyses restricted to nonsmokers (RR = 0.5; 95% CI 0.3-1.0) and cases younger than age 75 years (RR = 0.5; 95% CI 0.3-0.9). Incidence rates were not notably affected when analyses were restricted to cases that occurred more than 5 years after uric acid measurement (RR = 0.6; 95% CI 0.4-1.0). Inclusion of known or computed correlates of uric acid in regression models did not substantially change risk of IPD. This study provides prospective evidence of an association between uric acid and reduced occurrence of IPD and indicates that further investigations of this association are warranted.