With prospective observations we have documented by fluorescein angiography the development of retinal neovascularization in the eyes of patients with sickle cell-hemoglobin C disease (hemoglobin SC). In each patient, arteriolarvenular (AV) anastomoses occurred before the development of neovascular sea fans. To our knowledge, this report constitutes the first such documentation in the literature. New sea fans from AV anastomoses appeared throughout an average interval of 18 months (range, 8 to 36 months) in approximately 21% of young adults with hemoglobin SC. Each year approximately 14% of young patients with hemoglobin SC may develop retinal neovascularization.