The phenothiazine dixyrazine (5 mg . kg-1 i.v.) had minimal, transient hypotensive effects but significantly reduced the leakage of 125I labelled serum albumin in conscious rats subjected to acute hypertension provoked by i.v. adrenaline or bicuculline. By contrast, dixyrazine did not protect the blood-brain barrier during osmotic stress induced by intracarotid infusion of 2 M urea. The diameters of pial arteries and veins were continuously measured with a multichannel videoangiometer through a closed cranial window in anesthetized rats before and after i.v. injection of dixyrazine (5 mg . kg-1). No change in vessel diameter was observed except for a transient autoregulatory dilatation of arteries in response to a slight transitory decrease in the blood pressure. It is concluded that dixyrazine probably protects the blood-brain barrier during mechanical stress by modifying the endothelial cell membrane.