This review addresses the long-standing controversy over the principal mechanisms of transport of macromolecules through the endothelium of microvessels of ‘normal’ permeability. Two types of mechanism have been proposed: convective transport through ‘large pores’ in the endothelium; transport via vesicles (transcytosis). The different techniques for estimating microvascular permeability to macromolecules are described and values for microvascular permeability to serum albumin in different tissues are tabulated. Whereas the evidence for convective transport when obtained from experiments on perfused microvascular beds remains convincing, attention is drawn to recent measurements using the tracer uptake technique which suggest that transport in the intact circulation from blood to tissues may not be coupled to fluid movement. Direct evidence for the involvement of endothelial vesicles in transendothelial transport has been reported relatively recently but the mechanisms whereby macromolecules are conveyed through the vesicular system have yet to be established. The possibility of convective transport through transient transendothelial channels formed by the fusion of vesicles is discussed.

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