In an association study, the relationship between the insertion/deletion (I/D) plasminogen activator inhibitor 1 (PAI-1) gene polymorphism or the I/D angiotensin 1-converting enzyme (ACE) gene polymorphism and the development of diabetic retinopathy in patients with type 2 diabetes was investigated. One hundred and twenty-four subjects with type 2 diabetes and diabetic retinopathy were compared to 80 diabetic subjects without retinopathy with diabetes of a duration of more than 10 years. The PAI-1 gene distribution and ACE gene distribution in patients with diabetic retinopathy (4G4G 31.4%, 4G5G 46.8%, 5G5G 21.8%; DD 26.6%, ID 50.8%, II 22.6%) were not significantly different from those of diabetic subjects without retinopathy (4G4G 31.3%, 4G5G 50%, 5G5G 18.7%; DD 31.3%, ID 40%, II 28.7%). Neither the 4G/5G PAI-1 gene polymorphism nor the I/D ACE gene polymorphism contributed to the genetic susceptibility to diabetic retinopathy, either non-proliferative, proliferative or severe proliferative diabetic retinopathy, i.e. visual acuity of 0.1 or less in the better eye, in a group of Caucasian subjects with type 2 diabetes.