The objective of this study was to examine the cerebral circulation during spontaneous migraine attacks and to compare changes to an experimental headache model induced by nitroglycerin (NTG) infusion. This prospective study was carried out in a tertiary care hospital on migraineurs with or without aura. Healthy volunteers served as controls. There were no interventions. Flow velocity (FV) and pulsatility index (PI) were measured in migraineurs between and during headache attacks. In controls, FV and PI of the middle cerebral arteries were performed at baseline and after each IV infusion of 0.125, 0.25 and 0.5 microg/kg/min of NTG. In migraineurs, a significant increase in the mean flow velocity (MFV) in the left vertebral artery (VA) and the PI of the right VA during spontaneous migraine headache was found. In controls, all FV significantly decreased after infusion of NTG. The NTG model produces expected and substantially different vascular effects than those seen with spontaneous migraine headache.