Because the cause of stroke during migraine is not known, we studied 22 (17 females, 5 males; mean age, 32.7 years) classic migraine sufferers who had an ischemic stroke during an attack of migraine, with CT, Doppler ultrasound, cerebral angiography, and two-dimensional echocardiography. We found no cardiac or arterial lesion in 91% of the patients, as compared with 9% of age- and sex-matched migraineurs with stroke remote from a migraine attack and 18% of age- and sex-matched nonmigraineurs with stroke (p less than 0.00001). Mitral valve prolapse, arterial dissection, and vasospasm were not significant causes of stroke during migraine. These patients had longer previous attacks of migraine and their infarct was more frequently in the territory involved during the attacks than the controls, supporting the hypothesis that a prolongation of the migrainous process beyond usual limits may explain most migraine strokes.