We tested the hypothesis that the effective oncotic force that opposes flui
d filtration across the microvessel wall is the local oncotic pressure diff
erence across the endothelial surface glycocalyx and not the global differe
nce between the plasma and tissue. In single frog mesenteric microvessels p
erfused and superfused with solutions containing 50 mg/ml albumin, the effe
ctive oncotic pressure exerted across the microvessel wall was not signific
antly different from that measured when the perfusate alone contained album
in at 50 mg/ml. Measurements were made during transient and steady-state fi
ltration at capillary pressures between 10 and 35 cmH(2)O. A cellular-level
model of coupled water and solute flows in the interendothelial cleft show
ed water flux through small breaks in the junctional strand limited back di
ffusion of albumin into the protected space on the tissue side of the glyco
calyx. Thus oncotic forces opposing filtration are larger than those estima
ted from blood-to-tissue protein concentration differences, and transcapill
ary fluid flux is smaller than estimated from global differences in oncotic
and hydrostatic pressures.