Experimental gliomas were induced in rats by prenatal exposure to ethyl nitrosourea. Changes in the blood-brain barrier were determined by the uptake of a water-soluble compound, 99mTc-glucoheptonate. Increased uptake of 99mTc-glucoheptonate was measured in intact tumors and in various sectors of dissected tumors. The extent of 99mTc-glucoheptonate uptake greatly varied among different tumors and among different sectors of the same tumor. Ultrastructural and cytochemical analysis of the capillary endothelial wall revealed major alterations in tight junctions, which became permeable to horseradish peroxidase. In brain tissue around the tumors, uptake of 99mTc-glucoheptonate and ultrastructure of tight junctions were comparable to normal brain capillaries. The results of the present study indicate that altered endothelial tight junctions may provide the main route of transport of 99mTc-glucoheptonate through the endothelial wall.