Macular edema can contribute to visual loss in the retinitis pigmentosa (RP), but the sites and mechanism of blood-retina1 barrier (BRB) breakdown leading to macular edema are not known. An understanding of the mechanisms involved could lead to the design of effective pharmacologic therapy to prevent or minimize macular edema in RP. To investigate this problem, immunohistochemical staining for albumin was performed on paraffin sections of 22 normal and 29 RPaffected eyes. Specimens were graded for extent of albumin extravasation in different regions of the retina, optic nerve head, ciliary body, and iris. Electron microscopic immunocytochemical staining for albumin was performed on an additional 6 normal and 9 RPaffected eyes. Two-thirds of the eyes from patients with RP and no other ocular disorders demonstrated extravascular albumin in the inner portion of the posterior retina. This was evident even in the absence of cystoid macular edema (CME), but eyes that had CME showed extensive BRB failure. In some cases, passage of albumin from the choroid to the retina was prevented even in the absence of the retinal pigment epithelium (RPE). Electron microscopic immunocytochemistry revealed that albumin permeated retinal vascular endothelial cells and RPE cells that showed degenerative changes in RP.