Inverse aqueous size exclusion chromatography (SEC) was adopted to measure the permeability of microcapsules (hollow hydrogel spheres with diameter < 1 mm) using dextran molecular weight standards. Alginate/poly(L-lysine)/alginate microcapsules were chosen as a column substrate. Data from column SEC experiments were verified by kinetic studies of solute size exclusion. The permeability of tested microcapsules was modified by the reaction time with 0.05wt.% poly(L-lysine) (PLL). The exclusion limit of the microcapsules prepared at 5-min reaction time was found to be 100,000, while the microcapsules that were allowed to react with PLL for 20 min became less permeable and their exclusion limit was approximately 50,000. Based on relationships between solute size and molecular weight, the exclusion limits determined with dextrans were converted to the size and approximate molecular weight of protein presumably excluded by the capsular membrane at "ideal" conditions. The results from both column SEC and batch experiments suggest that the standard alginate/PLL/alginate capsules are permeable to immunoglobulins of IgG class. Unlike other techniques which utilize only a limited number of solutes, inverse SEC enables one to examine the capsule permeability to a homologous series of molecular weight standards. Inverse SEC also provides an opportunity to evaluate the properties of a large series of capsules directly by comparing their calibration curves. In addition, undesirable enthalpic effects in permeability studies with globular proteins as test solutes can be minimized or eliminated by using the inert molecular weight standards such as polysaccharides.