Stroke during sleep is an unexplored area of vascular neurology and its pathogenesis; clinical significance and prevention still remain uncertain. The aim of our study was to determine the epidemiological and clinical patterns of ischemic stroke occurring during sleep. Consecutive patients (n = 1822) with acute ischemic stroke recorded in the Tel Aviv Stroke Register were studied. Stroke during sleep was determined whenever focal neurological deficit was verified to have occurred while the patient had been asleep. The comparisons between patients with stroke during sleep and while awake were performed using the t test with Bonferroni correction and the chi(2) test for age, sex, vascular risk factors (i.e. ischemic heart disease, myocardial infarction, atrial fibrillation, arterial hypertension, hyperlipidemia, diabetes mellitus, peripheral vascular disease, smoking), vascular distribution (carotid versus vertebrobasilar) and severity of stroke (mild, moderate or severe). Data regarding the onset of stroke (during sleep or while awake) were available for 1,671 patients. A minority of strokes occurred during sleep (n = 311, 18.6%), and stroke during sleep was severer (chi(2) = 11.9, p < 0.002). No significant differences were found in terms of age, sex and vascular distribution between the two groups. None of the vascular risk factors was found to be more frequent in stroke during sleep. Strokes occurring during sleep were found to be severer than those with onset while awake. However, no specific clinical patterns of risk factor profiles could be identified in these patients. Hemodynamic factors may play an important role in the occurrence of stroke during sleep, and this issue should be further investigated.