Plasma levels of homovanillic acid (pHVA) following debrisoquine (DBQ) administration may be indicative of central dopaminergic activity. The effect of DBQ (10–20 mg) administration on pHVA in young healthy volunteers was studied to establish a protocol for use in de novo patients with Parkinson's disease. Subsequently, pHVA in de novo patients with Parkinson's disease were measured and compared to young healthy volunteers. Following DBQ (10 mg) administration to healthy volunteers, pHVA fell with time to a maximum of 62% of control values at 6 h. The decrease in pHVA was not affected by loading with DBQ (10 mg) 10 h previously (pHVA: 67.6 ± 5.8% of preDBQ levels) or increasing the dose to 20 mg (56.1 ± 11.8% of preDBQ levels) compared to a single 10 mg dose of debrisoquine (66.5 ± 4.5% of preDBQ levels). pHVA was reduced in both de novo patients with Parkinson's disease and in healthy volunteers following DBQ (10 mg) administration. However, there was no difference in pHVA before or after DBQ administration when comparing the two groups. These results suggest that, following DBQ administration, pHVA does not reflect dopamine neuronal loss in de novo patients with Parkinson's disease, so it is unlikely to detect the disease before the clinical symptoms manifest themselves.