Thirty-one (16 women, 15 men; mean age 68 years) of 1,000 consecutive patients with an ischemic stroke investigated systematically with computed tomography (CT), Doppler, electrocardiography (ECG), and biological tests had a diffuse hypodensity of the cerebral hemispheric white matter on CT, a sign indicative of leukoencephalopathy. In 25 of the 31 patients, the acute infarct was deep. Leukoencephalopathy was more frequent in patients with a deep infarct (8%) than in patients in whom the cortex was involved (0.8%) (p less than 0.01). A history of progressive intellectual impairment (23%) and the finding of a mild or moderate impairment, or severe dementia (84%) were more frequent in study patients (p less than 0.05) than in 31 sex- and age-matched controls with an acute infarct of same size and topography but without leukoencephalopathy. A history of hypertension (81%) and high blood pressure on admission (166 +/- 19/96 +/- 12 mm Hg) were the most common risk factors and were more frequent in study patients (p less than 0.05) than in controls. On the other hand, study patients had a greater than or equal to 50% stenosis or occlusion of the carotid artery (13%) less often than controls (35%) (p less than 0.05). Diabetes (23%), elevated blood cholesterol (13%), hematocrit greater than 45% (23%), smoking (32%), and myocardial ischemia by history or ECG (45%) did not differ. These findings suggest that hypertension may be more strongly associated with leukoencephalopathy than with deep infarcts. In acute stroke patients, leukoencephalopathy on CT should not be considered a fortuitous finding.