Parkinson's disease (PD), multiple system atrophy (MSA) and pure autonomic failure (PAF) are neurodegenerative disorders frequently associated with orthostatic hypotension and syncope, though with different underlying mechanisms. Cerebral hemodynamic responses in these three neurodegenerative diseases are still incompletely studied and it is possible that they would be differentially affected. We measured blood flow velocity (BFV) in the middle cerebral artery (MCA) and vertebral artery (VA) in patients with these disorders and investigated whether cerebral vasomotor reactivity (VMR) differs in these three disorders. Twenty-four patients (9 with PD, 10 with MSA and 5 with PAF) were studied. VMR was assessed in the MCA and VA, using transcranial Doppler (TCD) and Diamox test (injection of 1 g acetazolamide i.v.) with the patients in a recumbent position. The percent difference between BFV before and after acetazolamide injection was defined as VMR% and the results were compared by ANOVA. The mean MCA and VA blood flow velocities were similar in the three disorders and within normal limits for our laboratory. The mean MCA VMR values were 37.5+/-24.0%, 27.9+/-28.0% and 38.0+/-33.9% in PD, MSA and PAF, respectively. The VA VMR values were 22.9+/-23.6%, 32.4+/-38.0% and 18.9+/-18.3%, respectively, with no significant differences between the groups. We conclude that BFV is normal in PD, MSA and PAF and that the VMR, as investigated by TCD and the Diamox test, did not disclose differences in cerebral vasomotor responses between these conditions.