Experimental brain tumors were produced in 20 cats by stereotaxic xenotransplantation of a blastomatous glial cell clone into the internal capsule of the left hemisphere. Ten of these animals were treated after 2 weeks with a single injection of 10 mg dexamethasone in crystalline suspension. Three weeks after xenotransplantation vascular permeability was studied by electron microscopy with horseradish peroxidase as the barrier tracer (four animals), and extravasation of serum proteins was visualized by immunohistochemistry, using an image processing system (16 animals). In animals used for immunohistochemistry, the water content of peritumoral brain tissue was also determined. In both treated and untreated animals, spherical tumors with a diameter of about 10 mm were present at the implantation site. Extravasation of horseradish peroxidase was detected only in the tumor, but there was accumulation of serum proteins both in the tumor and the peritumoral white matter. Edema, in consequence, originated mainly in the tumor from where it spread into the surrounding brain tissue. Corticosteroid therapy reduced the water content of peritumoral brain tissue but did not affect increased barrier permeability of tumor vessels, and only slightly improved peritumoral accumulation of serum proteins. It is concluded that amelioration of tumor edema by corticosteroids cannot result solely from tightening of the blood-brain barrier to circulating macromolecules but must be due to an active restoration of cerebral water homeostasis despite persisting serum protein extravasation.