We studied the excitability of the visual and motor cortex in 36 patients with frequent migraine without aura (30 women, mean age 38.6 +/- 10.0 years) before and after treatment with topiramate (100 mg/day) using transcranial magnetic stimulation. Treatment with topiramate resulted in reduction of both headache frequency (12.0 +/- 1.3 to 5.8 +/- 3.2 migraine days per month; P = 0.004) and cortical excitability: motor cortex thresholds increased on the right side from 43.8 +/- 7.5% to 47.7 +/- 9.2% (P = 0.049) and on the left side from 43.4 +/- 7.0% to 47.2 +/- 9.6% (P = 0.047), and phosphene thresholds increased from 58.9 +/- 11.1% to 71.2 +/- 11.2% (P = 0.0001). Reduction of headache frequency correlated inversely with an increase of visual thresholds and did not correlate with motor thresholds. The effect of topiramate in migraine prevention is complex and can not be explained simply by inhibition of cortical excitability.