We report the use of a new stable isotope-labeled form of levodopa (LD) to examine in vivo central LD metabolism in Parkinson's disease (PD). Eight patients representing a wide spectrum of disease severity were administered 50 mg of carbidopa orally followed in 1 hour by an intravenous bolus of 150 mg of stable isotope-labeled LD (ring-1',2',3',4',5',6'-(13)C6). Serial blood samples were taken every 30 to 60 minutes and a lumbar puncture was performed 6 hours after the infusion. The average percentage of labeled homovanillic acid (HVA) in lumbar cerebrospinal fluid (CSF) was 54% (SD, 9%; range, 34-67%). The mean CSF labeled HVA concentration was 34.7 ng/ml (SD, 20.2 ng/ml; range, 11.3-67.9 ng/ml). Area under the curve for labeled serum LD closely predicted CSF labeled HVA concentrations (r = 0.747, p = 0.033). Labeled CSF HVA levels did not significantly correlate with either quality or duration of response to the labeled LD dose. In a similar manner, labeled CSF HVA concentrations were not influenced by duration of disease or previous daily LD dosage. These findings support the hypothesis that levodopa-induced benefit in PD is not severely limited by a defect in central levodopa metabolism.