Hypervolemic infusion in rats of bis (3,5-dibromosalicyl) fumarate cross-linked hemoglobin (DBBF-Hb) to 40-60% of blood volume produced histologic lesions in retina which were not observed in rats similarly infused with human serum albumin or lactated Ringer's solution. Rats treated with 40% DBBF-Hb, exhibited intermittent zones of dense retinal pigmented epithelium while 60% DBBF-Hb animals exhibited severe inner retinal edema and retinal pigmented epithelium vacuolization, large focal zones of photoreceptor outer segment disruption and in one animal, subretinal hemorrhage. Light microscopic immunocytochemical evaluation of retinas with antibodies directed to human hemoglobin and albumin, showed the presence of both hemoglobin and albumin in this tissue. Transmission electron microscopy of the lesions demonstrated vacuolated retinal pigmented epithelial cells and large areas of focal photoreceptor outer segment disruption. We conclude that hypervolemic infusion disrupts the blood retinal barrier and that although both DBBF Hb and albumin cross, only hemoglobin produced damage in the retina.