In this study the human glyceryltrinitrate (GTN) model of migraine was for the first time used to test the effect of a prophylactic drug. We chose to test val proate due to its well documented effect as a migraine prophylactic drug. Effica cy of this compound would support the usefulness of the model in prophylactic an timigraine drug development. Twelve patients with migraine without aura were inc luded in a randomized double blind crossover study. Valproate 1000 mg or placebo was given daily, each for a minimum of 13 days. On the last treatment day of ea ch arm a 20 min intravenous infusion of GTN (0.25 μg/kg/min) was given. Headach e was registered for 12 h after the infusion and headache intensity was scored o n a scale from 0 to 10. Fulfillment of IHS criteria was recorded for 24 h. The m iddle cerebral arteries were evaluated by transcranial Doppler and the diameter of the superficial temporal and radial arteries were measured with high frequenc y ultrasound. GTN evoked migraine fulfilling IHS criteria 1.1 in 6 patients afte r placebo and in 2 patients after valproate (P=0.125). Including additionally 3 patients on placebo and 1 patient on valproate who felt they had suffered a migr aine attack, but who had as associated symptoms only photophobia or phonophobia, a significant reduction in the number of patients with induced migraine after v alproate was seen (P=0.031). Median peak headache intensity was 1 (range 0-9) a fter valproate compared to 4.5 (range 0-8) after placebo (P= 0.120). Pretreatme nt with valproate as compared to placebo reduced the velocity in both middle cer ebral arteries after GTN (left P = 0.021, right P = 0.031). No effect of valproa te was seen in the diameter of the superficial temporal artery (P = 0.781) or th e radial artery (P = 0.367) before or after GTN. The study indicates that a prop hylactic effect of valproate may be demonstrated using the GTN human migraine mo del. Although, all headache parameters were reduced after valproate compared to placebo, only one parameter was statistically significantly reduced probably bec ause of the small number of patients. The sizeof the effect was similar to that of valproate in clinical trials. The GTN model may therefore be a valid tool for testing new prophylactic antimigraine drugs. In this study the human glyceryltrinitrate (GTN) model of migraine was for the first time used to test the effect of a prophylactic drug. We chose to test val proate due to its well documented effect as a migraine prophylactic drug. Effica cy of this compound would support the usefulness of the model in prophylactic an timigraine drug development. Twelve patients with migraine without aura were inc luded in a randomized double blind crossover study. Valproate 1000 mg or placebo was given daily, each for a minimum of 13 days. last treatment day of ech ch arm a 20 min intravenous infusion of GTN (0.25 μg / kg / min) was given. Headach e was registered for 12 h after infusion and headache intensity was scored on scale from 0 to 10. Fulfillment of IHS criteria was recorded for 24 h. The m iddle cerebral arteries were evaluated by transcranial Doppler and the diameter of the superficial temporal and radial arteries were measured with high frequenc y ultrasound. GTN evoked migraine fulfilling IHS criteria 1.1 in 6 patients afte r placebo and in 2 patients after valproate (P = 0.125). Including additionally 3 patients on placebo and 1 patient on valproate who felt they had suffered a migraine attack, but who had associated symptoms only photophobia or phonophobia, a significant reduction in the number of patients with induced migraine after v alproate was seen (P = 0.031). Median peak headache intensity was 1 (range 0-9) a fter valproate compared to 4.5 (range 0-8) After placebo (P = 0.120). Pretreatme nt with valproate as compared to placebo reduced the velocity in both middle cer ebral arteries after GTN (left P = 0.021, right P = 0.031). No effect of valproa te was seen in the diameter of The superficial temporal artery (P = 0.781) or th e radial artery (P = 0.367) before or after GTN. The study indicates that a prop hylactic effect of valproate may be demonstrated using the GTN human migraine mo del. were reduced after valproa tThe size of the effect was similar to that of valproate in clinical trials. The size of the effect was similar to that of valproate in clinical trials. The GTN model may therefore be a valid tool for testing new prophylactic antimigraine drugs.