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THE objective of this article is to examine two complementary hypotheses that, together, describe the role of the intercellular junction in the regulation of capillary permeability. One hypothesis states that the permeability of capillaries with continuous endothelium is modulated by the area available for the diffusion of small solutes in the spaces between adjacent endothelial cells. The second hypothesis states that the entry of solute into the junctional pathway and the diffusion of solute within the junctional pathway are regulated by the size and distribution of a network of fibrous molecules within the wide part of the junction. Transport through the junction may also be modulated by charge and specific chemical interactions between the solute and side chains on the fibrous network. When evaluating recent research designed to test the two hypotheses, I will draw mainly on experimental data obtained on individually perfused capillaries in frog mesentery and frog muscle. For these capillaries, methods have been developed to measure the permeability properties of the capillary wall under conditions where the area for transcapillary exchange and the forces determining exchange across the capillary wall are directly measured. Many of the problems to be discussed in this review were identified first from experiments on the microvascular bed in whole organs. Studies based on single capillaries enable the mechanisms of exchange across the capillary wall to be studied directly, removing some of the uncertainties that arise when 1) microvessels, having a range of permeability properties, contribute to exchange in a whole microvascular bed, 2) it is not possible to obtain a precise measurement of exchange area, and 3) the forces determining exchange at the capillary wall (hydrostatic pressure difference, solute concentration difference) are estimated indirectly from measurements in large arteries and veins. For a review of the advantages and limitations of single capillary studies see

Determinants of capillary permeability: a review of mechanisms based on single capillary studies in the frog.