Background: Prostaglandin E2 (PGE2) has been suggested to play an important role in the pathogenesis of migraine. In the present experiment we investigated if an intravenous infusion of PGE2 would induce migraine-like attacks in patients with migraine.Methods: Twelve patients with migraine without aura were randomly allocated to receive 0.4 μg/kg/min PGE2 (Prostin E2, dinoprostone) or placebo over 25 minutes in a two-way, crossover study. Headache intensity was recorded on a verbal rating scale, middle cerebral artery blood flow velocity (VMCA) was measured by transcranial Doppler (TCD) and diameter of the superficial temporal artery (STA) was obtained by c-series scan (Dermascan C).Results: In total, nine migraine patients (75%) experienced migraine-like attacks after PGE2 compared to none after placebo (p = 0.004). Seven out of 9 (58%) patients reported the migraine-like attacks during the immediate phase (0-90 min) (p = 0.016). Only two patients experienced the delayed migraine-like attacks several hours after the PGE2 infusion stop (p = 0.500). The VMCA decreased during the PGE2 infusion (p = 0.005) but there was no significant dilatation of the STA (p = 0.850).Conclusion: The migraine-like attacks during, and immediately after, the PGE2 infusion contrast with those found in previous provocation studies, in which the other pharmacological compounds triggered the delayed migraine-like attacks several hours after the infusion. We suggest that PGE2 may be one of the important final products involved in the generation of migraine attacks.