AbstractA method is described for the determination of the permeability of the blood—joint barrier to specific plasma proteins, using the ratio of protein concentration in synovial fluid to that in plasma. The inadequacy of the ratio per se as a direct index of permeability is discussed. Permeabilities are evaluated for the normal and rheumatoid human knee. Permeability increases in the rheumatoid knee by approximately 6 times for albumin and over 40 times for macroglobulins. The effect of protein molecular dimensions upon permeability is analyzed. Permeability shows less dependence upon solute dimensions in the rheumatoid knee than in the normal knee, i.e., molecular selectivity is reduced. From these data and synovial morphology, a two‐membrane model of the blood—joint barrier is developed. The relative contribution of the component intimal and endothelial layers to the total barrier is found to depend upon solute dimen
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