Dynamic vaso-occlusive and vaso-proliferative events occur in sickle cell retinopathy. Using streptavidin peroxidase immunohistochemistry, we investigated changes in distribution and relative levels of components in the fibrinolytic system and growth factors in retina and choroid from 2 sickle cell patients: a 20 month old SS patient and a 54 year old SC patient. Antigen localization in the sickle cell patients was compared to localization from 2 non-sickle cell, non-diabetic control subjects. In the fibrinolytic system, tissue plasminogen activator (tPA) localization and immunoreactivity were comparable in all eyes, but plasminogen activator inhibitor-1 (PAI-1) immunoreactivity was elevated within the walls of retinal vessels in the sickle cell tissue. Immunoreactive fibrin was often observed within the lumen of retinal and choroidal vessels and in choroidal neo-vascularization (CNV) in sickle cell subjects. Blood vessels containing fibrin generally exhibited elevated PAI-1 immunoreactivity. Von Willebrand's factor (vWf) and basic fibroblast growth factor (bFGF) immunoreactivity in sickle cell patients were elevated in choriocapillaris and the walls of some retinal vessels. Transforming growth factor-beta 1 (TGF-beta 1) immunoreactivity was significantly lower in sickle cell choriocapillaris than in controls. In chorioretinal pigmented lesions of the SC patient, bFGF and TGF-beta 1, beta 2, and beta 3 immunoreactivity was present within migrating retinal pigment epithelial (RPE) cells. Our interpretation of the data presented in this case study is that fibrin deposition within retinal and choroidal vessels of sickle cell subjects may occur due to elevated PAI-1 activity. Moreover, vaso-occlusions of choroidal vessels may influence the expression of growth factors in choriocapillaris endothelium, which could stimulate formation of choroidal neovascularization. Finally, fibrosis and gliosis in and near chorioretinal pigmented lesions may be stimulated by RPE production of bFGF and TGF-beta's.