Human retinal pigment epithelial (RPE) cells in culture, when overlaid by a fibrin clot, lose their normal epithelial morphologic features and migrate into the overlying clot as fibrocytelike cells. The behavior of human RPE cells on exposure to fibrin correlates well with the observed response of RPE in several ocular disorders in which fibrin deposition within the eye is an important feature. The mechanism of recognition and interaction between fibrin and RPE cells is unknown. The in vitro system used in our current studies allows the investigation of this interaction in a controlled environment. Further study of the interaction between human RPE cells and fibrin offers the possibility of improving our understanding and treatment of several blinding ocular disorders, including the disciform phase of senile macular degeneration, proliferative vitreoretinopathy, and the sequelae of ocular trauma.