Osmotic modification of the blood-brain barrier (BBB) provides an experimental model of vasogenic edema, is totally reversible, and does not cause any structural damage. In the present communication, the effect of corticosteroids on drug delivery to normal rat brain was evaluated in this model. Intraperitoneal dexamethasone was administered at doses ranging from 12 to 48 mg/sq m for 3 days; gentamicin delivery to the brain was then evaluated after either intravenous or intracarotid administration in both control and BBB-modified animals. Only animals receiving the highest dose of dexamethasone and in which the gentamicin was given intravenously demonstrated a statistically significant decrease in drug delivery. The effect of dexamethasone over a wide range of dosages, therefore, exhibited only modest effects on drug delivery to normal brain after osmotic BBB disruption.