Retinal microvascular abnormalities were evaluated in 74 insulin-dependent diabetic youths by fluorescein angiography on two or more occasions spanning at least 4 years. Half of this group showed progression of the retinal vascular abnormalities from a stage of no significant abnormalities to at least background retinopathy with more than ten microaneurysms. Proliferative retinopathy requiring laser photocoagulation occurred in 14% (10/74). Insulin administration (once or twice a day) and glycemic control as reflected by hemoglobin A1C were identical in those with progression and in those with no progression of retinopathy. More females than males in this age group developed progressive retinopathy (P less than .036). Human lymphocyte antigen (HLA) types DR3 and DR4 in combination occurred more frequently (P less than .001) in those with progression of retinopathy than in those without progression. Teenaged , female, insulin-dependent diabetics with both HLA DR3, and DR4, were at increased risk for developing proliferative retinopathy.