In this clinical study of the natural history of proliferative retinopathy in sickle cell-hemoglobin C disease, 25 eyes were observed without therapeutic intervention for an average duration of 31 months (range: 6 to 77 months). A new ophthalmoscopic and angiographic classification allowed quantitative assessment and comparison of these eyes at the beginning and at the end of the observation period. Clinically symptomatic and significant stages of proliferative sickle retinopathy (PSR) were frequently observed in patients between the ages of 20 and 30. All stages of PSR appeared to progress. This seemed particularly true of that stage characterized by spontaneous vitreous hemorrhages; ie, 28% of eyes had evidence of vitreous hemorrhage initially, whereas 44% of the same eyes had similar evidence at follow up. No proliferative lesions were seen to regress.