The exact mechanism of action of beta blockers in migraine remains undetermined. An effect on the central nervous system (CNS) might be a factor. The evidence from the literature indicates that the anatomical and chemical targets for these drugs are present in the mammalian brain, that they readily penetrate the brain, and that they may modify CNS functions. The present study shows that psychomotor tests and contingent negative variation (CNV), an event related slow cerebral potential, both of which are abnormal in untreated migraineurs, tend to normalize after treatment with the beta blocker metoprolol. Moreover, a strong positive correlation was found between the amplitude of CNV and the clinical efficacy of beta blockers in migraineurs. One might hypothesize that a hyperactive central catecholaminergic state in migraine might be the common denominator between reduced performance on psychomotor testing and enhanced CNV. It remains to be determined whether this is due to hyperactivity of catecholaminergic neurons or to hypersensitivity of catecholamine receptors.