We have investigated the ultrastructure of the intercellular clefts of the walls of single capillaries and venules of the frog mesentery in which the hydraulic permeability (Lp) and the reflection coefficient of the vessel walls to serum albumin (sigma BSA) had been measured using the micro-occlusion technique of Michel (1980). Our aim was to investigate whether the dimensions of the clefts were sufficient to accommodate the pathways through the vessel walls necessary to account for the measured permeability. 2. Lp was measured in seventeen individually perfused vessels. The walls of fourteen of these were relatively impermeable to macromolecules with a sigma to albumin greater than 0.66 (mean value 0.83, S.E.M. +/- 0.04). The Lp of these fourteen vessels ranged from 1.8 x 10(-7) to 12.5 x 10(-7) cm s-1 cmH2O-1 and had a mean value of 5.9 (S.E.M. +/- 0.85) x 10(-7) cm s-1 cmH2O-1. 3. Cleft dimensions estimated from electron micrographs of 642 transversely sectioned endothelial cell junctions from the same seventeen vessels gave a value for the mean cleft width (W) of 0.0220 micron (S.E.M. +/- 0.0064 micron). The mean depth of the clefts from luminal to abluminal surface of the endothelium (delta x) was 0.395 micron (S.E.M. +/- 0.091 micron) with a range of 0.104-1.70 micron. The cleft length per unit area of cell wall (L), calculated using the formulation of Bundgaard & Frøkjaer-Jensen (1982), was 2064 (S.E.M. +/- 112) cm cm-2. Measurements were also made of cleft dimensions from longitudinally sectioned junctions from five of the seventeen vessels. 4. The fraction of the surface area of capillary wall occupied by the clefts (Ap = LW) had a mean value of 0.0048 (+/- 0.00014) for all seventeen vessels with a range of 0.0030-0.0074 when estimated from transverse sections. There was no correlation between the variation of Lp between different vessels and the variations of Ap. 5. Data from the fourteen vessels when sigma BSA was greater than 0.66 revealed a correlation between values of Lp and the reciprocal of delta x (r = 0.6675, P less than 0.01). No correlation was found between Lp and the mean thickness of the endothelial cells in the vicinity of the clefts. This is strong evidence for the intercellular cleft being the principal pathway for fluid movements. Variation in cleft depth appears to be a factor determining variation in permeability between different capillaries.(ABSTRACT TRUNCATED AT 400 WORDS)
