Diffusivities of fluorescein-labeled macromolecules were measured in dilute aqueous solution (D-infinity), agarose gels (D-a), and agarose-dextran composite gels (D) using fluorescence recovery after photobleaching. Macromolecules with Stokes-Einstein radii (r(s)) ranging from 2.7 to 5.9 nm were used, including two globular proteins (ovalbumin and BSA) and three narrow fractions of Ficoll, a spherical polysaccharide. Gels with agarose volume fractions of 0.040 and 0.080 were studied with dextran volume fractions ranging from 0 to 0.0076 and 0 to 0.011, respectively. For both agarose concentrations, the Darcy permeability (kappa) decreased by an order of magnitude as the dextran concentration in the gel was increased from zero to its maximum value. For a given gel composition, the relative diffusivity (D/D-infinity) decreased as r(s), increased, a hallmark of hindered diffusion. For a given test molecule, D/D-infinity was lowest in the most concentrated gets, as expected. As the dextran concentration was increased to its maximum value, two- to threefold decreases in relative diffusivity resulted for both agarose gel concentrations. The reductions in macromolecular diffusivities caused by incorporating various amounts of dextran into agarose gels could be predicted fairly accurately from the measured decreases in kappa, using an effective medium model. This suggests that one might be able to predict diffusivity variations in complex, multicomponent hydrogels (such as those in body tissue) in the same manner, provided that values Of K can be obtained. (C) 2004 American Institute of Chemical Engineers.