VVOs [13] are large collections of vesicles and vacuoles focally dis tributed in venule endothelial cytoplasm, often in a parajunctional location (fig. 104, 105). In standard, single electron microscopic sections (70-to 80-nm), their individual components number from several to hundreds [13, 14]. Connections to luminal, abluminal and lateral plasma membranes can be found in these single sections. In some single sections these were interconnected as complex transcellular structures. When the individual parts of VVOs in control vessels (fig. 105, 106) and tumor vessels were quantified, they were the same [13]. Morphometrics (shape-factor analysis) showed that the shape of individual units of VVOs was more variable in tumor-associated vessels than in control vessels [13, 14]. The size of individual vesicles and vacuoles of tumor and control venular VVOs was more variable than the more uniform size of caveolae in capillaries [15]. An analysis of size distributions of the vesicles and vacuoles comprising VVOs uncovered a modal distribution [108, 346–348] comprised of multiples of the smallest, unit-sized vesicle, such that the increasing size of each mode could be accounted for by fusions of the smallest vesicles [349]. This unit vesicle size was identical to that of capillary caveolae [349]. Thus, a powerful mathematical analysis supports formation of VVOs in tall venular endothelium from multiple fusions of individual caveolae–a process that is generally lacking in thin capillary endothelia. Direct examination of single ultrastructural sections of standard thickness allows one to define individual anatomic components of the vesicles and vacuoles that comprise VVOs. Thus, they open to endothelial cell surfaces (luminal, abluminal, lateral) by stomata which are guarded by a thin, electron-dense diaphragm (fig. 106)[13, 14]. Interconnected parts also are joined by stomata and diaphragms, and larger structures have multiples of such structures. Narrow necks provide 11-nm-wide channels from stomata to single vesicles or between stomata of adjacent vesicles and vacuoles [14]. These substructures