Brain and retinal infarctions during sleep have been attributed to focal hypoperfusion caused by systemic hypotension combined with underlying arterial stenosis, rather than to embolism. Because some retinal emboli may be visualized on ophthalmoscopy, we studied 24 consecutive patients (18 men and six women) aged 26-78 (mean 58) years with recent retinal infarction and determined whether the infarction had occurred during sleep or wakefulness. All patients underwent dilated ophthalmoscopy and a carotid artery study (arteriography in 20, duplex ultrasound in the remaining four), and 12 had echocardiography. Retinal infarction occurred during sleep at an unexpectedly rate (14 of 24 observed compared with eight of 24 expected, p = 0.02). Retinal cholesterol emboli were seen in one half of the patients regardless of whether the retinal infarction had occurred during sleep or wakefulness. Carotid artery disease was found in seven of the 14 patients in whom infarction had occurred during sleep and in eight of the 10 patients in whom infarction had occurred during wakefulness (p = 0.21). Cerebrovascular occlusive disease was not found in the five patients aged less than 50 years. Our findings suggest that embolism is a common mechanism of retinal infarction during sleep or wakefulness, that in patients aged greater than 50 years extracranial carotid artery disease is a common source of retinal emboli, and that the retina may be especially susceptible to infarction during sleep.