To identify risk factors for the development of proliferative diabetic retinopathy, we compared 111 patients with longstanding insulin-dependent diabetes who had proliferative retinopathy (cases) with 81 patients with diabetes of similar duration (an average of 26 years) who did not have proliferative diabetic retinopathy (controls). The cases had diabetes that was more difficult to manage, as evidenced by their more frequent blood sugar levels above 200 mg per deciliter (11 mmol per liter) on routine clinic visits (odds ratio, 1.6 for each increment of 10 per cent in the relative frequency), and they expended less effort in managing their diabetes, as indicated by their less frequent testing of urine for sugar (odds ratio, 0.3). Among those who did not have myopia, the cases also had an excess of the HLA-DR phenotypes 4/0, 3/0, or X/X (odds ratio, 10.0). Among those with myopia, these phenotypes did not carry an increased risk of proliferative retinopathy. These results support a multifactorial model for the development of proliferative diabetic retinopathy; however, the mechanisms of action of the identified factors remain unknown.