The blood-brain barrier (BBB) was studied in rats with electrolyte-induced demyelination (EID), an experimental model for central pontine myelinolysis. Intravenously injected peroxidase was extravasated at 3 h post hypertonic saline injection (PHS) into regions frequently involved in EID. Increased pinocytotic activity and focal interendothelial gaps were seen at 3 h PHS and less frequently at 48 h PHS. Measurement of total cerebral water content revealed an increase during the hyponatremic phase. This was followed by a marked increase at 3 h PHS with continued increment at 48 h PHS. Intracellular edema with accumulation of fluid within neurites and astrocytic processes was noted during the hyponatremic phase, whereas extracellular edema developed after hypertonic saline injection. The implications of disrupted BBB and its role in the pathogenesis of EID are discussed.