Since the brain 5HT(2) receptors might be implicated in migraine pathogenesis, we have used positron emission tomography and F-18-fluorosetoperone, a 5HT(2) specific radioligand, to investigate in vivo the cortical 5HT(2) receptors in migraine subjects. Nine migraineurs who had either migraine with and without aura (n = 5) or only migraine without aura (n = 4) were studied between attacks. Twelve unmedicated healthy subjects of similar mean age were used as controls. Brain radioactivity was measured after F-18-setoperone IV injection for 90 min. A decrease of the regional specific distribution volumes (SDV) of the ligand was observed both in migraineurs and in controls. The age adjusted group means of SDV did not differ between patients and controls for the whole and for the right or left frontal, temporal, parietal and occipital cortex. These results suggest that cortical 5HT(2) receptors may be unaltered between attacks in migraine sufferers.