Cortical biopsies of 17 patients with diagnoses of congenital malformation, cerebral tumor or brain trauma complicated by subdural hematoma or hygroma were studied with the electron microscope; the alterations of the blood-brain barrier in moderate and severe perifocal cerebral edema were observed. Moderate edema was found associated with central nervous system malformations, while severe edema was seen accompanying brain tumors and serious head injuries. The peripheral cytoplasm of endothelial cells displayed increased formation of microvilli and clear or amorphous electron-dense vacuoles, as well as pinocytotic and coated vesicles. In severe edema, the formation of elongated or chained vacuoles forming transendothelial channels was observed. In moderate edema, endothelial junctions exhibited a tortuous pathway, with a luminal portion sealed by tight junctions and dilated, open, basal portions ending at the basement membrane. In severe edema, the zonulae accludentes partially disappeared and the endothelial junction basal segments became irregularly dilated. The basement membrane showed enlargement, rarefaction, vacuolization, and the presence of collagen fibers. Fine expansion of the basement membrane was distinguished, showing matrix loss and clear, irregularly-dilated channels. Capillaries with reduplicated basement membrane were also observed. The pericytes exhibited edema, vacuolization, and phagocytic activity. In moderate cerebral edema, the clear or dense edematous and vacuolated perivascular end-feet of astrocytes appeared closely applied to the basement membrane, while in severe cerebral edema, they were separated from the basement membrane and showed gradual disappearance of the gap junctions. In all cases, moderately or markedly dilated extracellular spaces were observed in the pericapillary neuropil.