Histopathological sequelae of the osmotic blood-brain barrier opening were studied in 69 adult Wistar rats sacrificed between 2 minutes and 6 days after infusion of 1.6 M mannitol into the unilateral internal carotid artery. The results were correlated with immunohistochemical localization of autologous albumin in the brain parenchyma on paraffin sections. Extravasation of serum albumin was evident in all rats, and the albumin immunoreactivity, commonly localized to the territories of the ipsilateral anterior, middle, and posterior cerebral arteries and contralateral anterior cerebral artery, showed maximum intensity in the rats sacrificed 30 minutes after infusion. The albumin immunoreactivity remained macroscopically visible in the brain parenchyma for 24 to 48 hours, and then gradually faded out. Serum extravasation was accompanied by widening of the perivascular space and focal edema, which largely subsided within 48 hours as the albumin immunoreactivity of the tissue diminished. Although no overt neurological sequelae were seen in the present experiment, minute but definite foci of infarction with focal accumulation of albumin were found in 23 (38%) of 61 rats surviving more than 30 minutes. In addition, ischemic neuronal death of delayed onset was encountered among neurons in the CA-1 region of the hippocampus, in the cerebellum, and in the thalamus in five (25%) of 20 rats sacrificed between Days 4 and 6. Thus, care should be exercised in the practice of this procedure.