BACKGROUND: Among serotonin receptors, 5-HT(1A) receptors are implicated in the regulation of central serotoninergic tone and could be involved in the abnormal brain 5-HT turnover suspected in migraineurs. The aim of this study was to investigate 5-HT(1A) receptors' availability during migraine attacks. METHODS: Ten patients suffering from odor-triggered migraine attacks and 10 control subjects were investigated using positron emission tomography (PET) and [(18)F]MPPF PET tracer, a selective 5-HT(1A) antagonist. All subjects underwent calibrated olfactory stimulations prior to the PET study. RESULTS: Four patients developed a migraine attack during the PET study. In these patients, statistical parametrical mapping and region of interest analyses showed an increased [(18)F]MPPF binding potential (BP(ND)) in the pontine raphe when compared to headache-free migraineurs and control subjects. This ictal change was confirmed at the individual level in each of the four affected patients. In comparison with the headache-free migraineurs, patients with a migraine attack also showed significantly increased [(18)F]MPPF BP(ND) in the left orbitofrontal cortex, precentral gyrus and temporal pole. No significant change in [(18)F]MPPF BP(ND) was observed between headache-free migraineurs and controls. CONCLUSIONS: Our results emphasize the role of 5HT(1A) receptors in the pontine raphe nuclei during the early stage of migraine attacks.