Through the first 2 hr, uptake of [Tc-99m]pertechnetate and of Co-57 bleomycin were assessed in 29 brain tumors and were correlated with the ultrastructure of the tumor's capillary endothelium. No difference in uptake was found between the two tracers. Permeability of brain tumors to these agents was found to be governed by the same ultrastructural features that determine permeability in experimental brain tumors: the type of junction between contiguous endothelial cells in the capillaries. Meningiomas, which showed very high uptake of the radiotracers, demonstrated open or punctate junctions with short fusion of apposed membranes. They also showed a large number of pinocytotic vesicles and fenestrae. Capillaries of tumors without uptake had a small number of short tight junctions (less than 0.25 mu) between adjacent endothelial cells and a relatively large number of long junctions (greater than 0.5 mu). In intracerebral tumors that showed relatively high uptake, the reverse was true: most of the junctions were short and only a few long junctions were found. That uptake of [Tc-99m]pertechnetate and of Co-57 bleomycin depends on tumor capillary ultrastructure (which determines the permeability) suggests the possibility of the use of radiopharmaceuticals as in vivo indicators of tumor permeability. Brain scintigraphy may help to asses brain-tumor availability to non-lipid-soluble chemotherapeutic drugs.