Thirty-four percent of 182 ischemic stroke patients registered during 1 year in a prospective hospital stroke data base complained of headache within a 72-hour interval of stroke onset. Headache was more common in patients under 70 years of age, in nonsmokers, in those with a past history of migraine, and in subjects presenting transient loss of consciousness, nausea/vomiting, or visual field defects. Headache was more frequent in vertebrobasilar (57%) than in carotid (20%) territory strokes, more so in posterior cerebral artery (90%) and cerebellar infarcts (80%), and was infrequent in subcortical infarcts (7%) and lacunes due to single perforator disease (9%). In multiple regression analysis, vertebrobasilar stroke (odds ratio 6.9), lacuanr stroke (odds ratio 0.06), and past history of migraine (odds ratio 6.7) were significant independent predictors of headache, suggesting that ischemic stroke location is the major determinant of stroke-associated headache, most probably related to activation of the trigeminovascular system, whose threshold may be modified by individual susceptibility.