We used cationized ferritin, which binds to negatively charged membrane surfaces, as a tracer to delineate the aqueous humor outflow pathway by perfusing it into the anterior chamber of 14 normal human eyes and five with primary open angle glaucoma. In the normal human eyes, diffuse labeling with cationized ferritin was evident throughout the outflow pathway, while in the glaucomatous eyes distinctly different staining patterns were noted. A decorating pattern similar to that seen in normal eyes was observed, as well as apparent areas of underperfusion, suggestive of possible segmental changes in aqueous outflow. These findings may support the hypothesis that primary open angle glaucoma is a segmental disease of the outflow system due to possible regional increases in resistance to aqueous outflow.