Secretion of plasminogen activators was examined in 11 cells cultures from subretinal fluid of patients with retinal detachment. The plasminogen activator production was compared to 4 retinal pigment epithelial cell cultures from post-mortem donors with no known retinal pathology. Plasminogen activator activity was evaluated by zymography and was corrected for the total cell protein in the cultures. Cells from subretinal fluid had more proteolytic activity and secreted more active urokinase-type plasminogen activator than retinal pigment epithelial cells of donor origin. It is possible that cells from subretinal fluid are modulated by the conditions in subretinal fluid to secrete more urokinase-type plasminogen activator, generally considered to be a sign of invasive growth or that the subretinal fluid cultures contain other cell types than solely retinal pigment epithelial cells, such as pigmented macrophages, with an active plasminogen activator production. Alternatively, retinal pigment epithelial cells detached into the subretinal fluid may represent a selected population of retinal pigment epithelial cells with a more active extracellular proteolysis.