The relationship of the osmotic pressure gradient between blood and brain, and the development of ischemic brain edema was studied. Focal cerebral ischemia was produced by left middle cerebral artery occlusion in rats. Brain osmolality was determined with a vapor pressure osmometer, brain water content by wet-dry weight, and tissue sodium and potassium contents by flame photometry. Permeability of the BBB was tested by Evans blue. Measurements were made from the ischemic cortex within 14 days of occlusion. Brain osmolality increased from 311 +/- 2 to 329 +/- 2 mOsm/kg by 6 h after occlusion. Serum osmolality did not change significantly. The osmotic gradient between blood and brain peaked at approximately 26 mOsm/kg. Brain osmolality then decreased to 310 +/- 2 mOsm/kg by 12 h after occlusion and remained at about that same level. Water content increased progressively within 1 day of occlusion, then gradually decreased by 14 days. Brain tissue sodium plus potassium content did not increase within 6 h of occlusion, and Evans blue extravasation was not seen within that time. These findings indicate that an osmotic pressure gradient contributes to the formation of edema only during the early stage of cerebral ischemia. Furthermore, the increase in brain osmolality is not related to tissue electrolyte change or BBB disruption to protein.