Purpose: To study cerebral vasoreactivity to hypercapnia in Parkinson's disease before and after L-DOPA administration. Methods: The prospective study was conducted in 20 patients presenting with Parkinson's disease, using 3T blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) covering the whole brain. The hypercapnic stimulus was block-designed using carbogen inhalation, a gas mixture of 7% CO2 and 93% O2, before (OFF) and 60 minutes after administration of a suprathreshold (120%) therapeutic L-Dopa dose (ON). Ten age-matched controls were enrolled for between-group comparisons. Analyses were conducted with a random effects model and corrected for multiple comparisons. Results: No adverse reaction to the hypercapnic stimulus was reported. However, 10 patients and 2 controls were excluded because of incomplete protocol realization, inappropriate hypercapnic stimulus, or excessive movements, leaving 10 patients and 8 controls for further analyses. The hypercapnic stimulus increased whole brain BOLD signal of 1.48±0.06% (mean ± standard error) in controls, 1.59±0.05% in patients OFF, and 1.62±0.09% in patients ON. Regions of interest analyses showed a signal increase in the grey matter of 2.60±0.16% in controls, 2.89±0.21% in patients OFF, and 2.87±0.12% in patients ON. No global or regional significant difference was detected when comparing patients OFF and ON L-Dopa, or between patients and controls. Conclusion: Contrary to Alzheimer's disease, the vasoreactivity to hypercapnia was normal in Parkinson's disease before and after L-Dopa administration compared to controls. This negative result is an important finding, especially for neuroscientists using fMRI to investigate motricity and cognition, discarding a significant confounding effect.