Vitreous and serum were obtained at the time of vitrectomy from 23 diabetic subjects with proliferative retinopathy and from 8 nondiabetic subjects. The mean concentration of IGF-I in vitreous from diabetic patients with neovascularization was 6.3 ± 0.93 versus 2.7 ± 0.96 ng/mi. Chi-square and rank analysis indicated that higher concentrations of IGF-I occurred in diabetic vitreous (P < 0.01 by both analyses). IGF-II concentrations in vitreous of control and diabetic subjects were not significantly different. A positive correlation existed between the concentrations of IGF-I and IGF-II in vitreous and their concentrations in serum in diabetic subjects, but not in control subjects. When vitreous concentrations of IGF-I were calculated for diabetic subjects studied previously with rapid acceleration of retinal disease, these concentrations varied from 20 to 30 ng/ml. The concentrations of IGF-I in the vitreous of most diabetic subjects with severe neovascularization are thus in the range known to stimulate cellular differentiation and growth in several systems. Whether they do so in the eye, and thus contribute to the development of retinopathy, remains to be determined.