Transferrin (TF) is the major transport protein involved in human iron metabolism. The expression of the cell-surface TF receptor is associated with cellular proliferation, the dominant feature of proliferative vitreoretinal disorders with traction retinal detachment. A total of 14 retinal membranes from patients with different clinical diagnoses contained immunoreactive TF. Expression of the cell-surface TF receptor was confirmed by a monoclonal anti-human TF-receptor antibody label in 11 of the 14 specimens. We developed a noncompetitive enzyme-linked immunosorbent assay (ELISA) for TF and found it to be a significant component of vitreal protein, with a level of 65.7 +/- 33.9 mg/l. Vitreal TF as a major iron acceptor probably has a protective function, but its interaction with macrophages and its growth-promoting activity may subsequently stimulate the proliferation of fibroblasts and retinal pigment epithelial cells.