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Concentration-time profiles of fluorescein isothiocyanate (FITC)-conjugated bovine serum albumin and a graded series of FITC-dextrans of 20,000-70,000 molecular weight were measured within the erythrocyte-free plasma layer in individual vessels and at various positions within the interstitial tissue space of mature granulation tissue grown in a rabbit ear chamber. Sodium fluorescein was used as a representative small molecule. The plasma pharmacokinetic data were found to follow a biexponential decay in time. A one-dimensional model of diffusion adequately described interstitial transport. Interstitial diffusion coefficients decreased progressively with Stokes-Einstein radius with values for albumin being significantly reduced from that for a dextran of equivalent hydrodynamic radius. Interstitial diffusion of sodium fluorescein and albumin agreed with a fiber-matrix model, whereas the interstitial diffusion of dextrans more closely corresponded to a pore model.