Some controversial issues exist whether regional cerebral blood flow (rCBF) changes are present both in migraine with and without aura during the interictal period. For this reason we have studied rCBF characteristics in migraine patients when headache-free. rCBF examinations were performed by the 133Xe inhalation method on 39 normal subjects (24 aged 45 or less and 15 older than 45), on 10 migraine patients with (A+) and on 10 without (A-) aura. The values of each patient were compared with the age-matched control population mean by a computer-assisted mapping system that allows statistical analysis in real time. To compare inter-individual variability 10 subjects, out of 39 normals, constituted an age-, sex- and CO2-matched control group (C). 8 A+ patients and 7 A- showed significant alterations of CBF in comparison with the age-matched control population. The analysis between the age-, sex- and CO2 matched groups showed significant differences of the inter-hemispheric (F = 6.669, p = 0.004) and of the frontal (F = 7.480 p = 0.0008) asymmetries. These data show that in the headache-free period a derangement of the cerebral perfusion is present in both migraine with and without aura, suggesting they are due to the same disease process. Furthermore they show the usefulness of a computer-assisted mapping system, suitable for clinical use, in discovering small alterations in cerebral perfusion.