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Extravascular transport of fluorescein isothiocyanate-conjugated bovine serum albumin and a graded series of fluorescein isothiocyanate-dextrans from Mr 19,400 to 71,800 were studied in both normal tissue (granulation) and tumor (VX2 carcinoma) grown in a rabbit ear chamber. Sodium fluorescein was used as a representative small molecule. A one-dimensional diffusion model adequately described extravascular transport in both normal and tumor tissue. Measured diffusion coefficients showed a relationship with molecular size which progressively deviates from that of free diffusion in water, with values for albumin being significantly reduced from that for a dextran of equivalent size. Macromolecular transport in tumor tissue was hindered to a lesser extent than in normal tissue, which is consistent with reports of reduced contents of glycosaminoglycans, and markedly large interstitial space in tumors. Diffusion coefficients for dextran were found to vary with molecular weight according to the expression, D = a(Mr)b, in both normal tissue (a = 10(6) and b = -2.96) and tumor (a = 2.51 X 10(-2) and b = 1.14).