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 bee
n proposed: convective transport through 'large pores' in the endothel
ium; transport via vesicles (transcytosis). The different techniques f
or estimating microvascular permeability to macromolecules are describ
ed and values for microvascular permeability to serum albumin in diffe
rent tissues are tabulated. Whereas the evidence for convective transp
ort when obtained from experiments on perfused microvascular beds rema
ins convincing, attention is drawn to recent measurements using the tr
acer uptake technique which suggest that transport in the intact circu
lation from blood to tissues may not be coupled to fluid movement. Dir
ect evidence for the involvement of endothelial vesicles in transendot
helial transport has been reported relatively recently but the mechani
sms whereby macromolecules are conveyed through the vesicular system h
ave yet to be established. The possibility of convective transport thr
ough transient transendothelial channels formed by the fusion of vesic
les is discussed.