We hypothesized that infusion of VIP may induce headache/migraine in migraineurs and that VIP-induced headache may be associated with dilation of intra- and extracranial vessels. To test this hypothesis, we performed a double blind placebo-controlled crossover study in migraineurs and studied the effect on headache and cerebral and systemic hemodynamic parameters. The subjects were randomly allocated to the infusion of 8pmol/kg/min VIP or placebo (isotonic saline), duration 25min. Headache intensity, mean velocity of blood flow in the middle cerebral artery (VmMCA), superficial temporal artery diameter, end-expiratory CO2 and vital signs were recorded at baseline and then every 10 min until 120 min after start of the infusion. The patients received a headache diary for the following 12 hours after infusion.