Rapid increases in microvascular permeability are associated with the appea
rance of openings in microvascular endothelium; which are believed to devel
op between the endothelial cells of venules. Reconstruction of these openin
gs, from electron micrographs of serial sections of the endothelium reveal
that many pass through the periphery of the endothelial cells close to inta
ct intercellular junctions. Transcellular pathways are the principal type o
f opening induced in microvascular endothelium by the ionophore A23187, by
VEGF, and by high transmural pressures. Some mediators induce the fusion of
vacuoles with the luminal and abluminal surfaces of the endothelium, and i
t is suggested that the transcellular openings may develop from vacuolar ch
annels.