Human pathologic specimens from eyes with several different disease processes were immunohistochemically stained with antisera directed against rat or human serum albumin. In 33 eyes with no known ocular disease and no pathologic abnormalities, positivity was seen in the choroid and within retinal vessels, but not within the retina, except in one case in which focal staining in an area of outer retina was noted. In eyes with a history of ocular disease and/or pathologic findings, extravascular albumin staining was seen in areas of the retina generally corresponding to pathologic abnormalities. Albumin in the inner retina appeared to emanate from retinal vessels, but often collected along the internal limiting membrane. Staining in the outer retina was frequently demonstrated along the external limiting membrane, but in some cases, was also seen between the photoreceptor outer segments and within the retinal pigment epithelium. Eyes with primary retinovascular disease showed staining more commonly in the inner retina (77%) than the outer retina (38%) as would be predicted on theoretical grounds, whereas eyes with other disease processes showed no difference in frequency of staining between inner and outer retina. These data suggest that immunohistochemical staining of extravascular albumin is a useful technique for localizing breakdown of the blood-retinal barrier and is applicable to several disease processes.