In order to evaluate if residual B-cell function is a protecting factor against the development of diabetic retinopathy in type I diabetics we measured C-peptide levels before and after glucagon stimulation (1 mg i.v.) in 74 type I diabetics. In all patients retinopathy was assessed by fluorescein angiography and retinal lesions were classified as: grade 0, normal; grade 1, background retinopathy; grade 2, proliferative retinopathy. We then correlated the degree of retinopathy to sex, age, duration of diabetes, smoking, percentage of ideal body weight, systolic and diastolic blood pressure, serum cholesterol, triglycerides, creatinine and C-peptide by means of multiple linear regression analysis. Twenty-three out of 74 type I diabetics had retinopathy. In all 7 subjects with proliferative retinopathy duration of diabetes exceeded 10 years. There was significant correlation between retinopathy and duration of diabetes (r = 0.373, p less than 0.001). No correlation was found between retinopathy and all the other variables, in particular between retinopathy and basal C-peptide or C-peptide increment (delta). An inverse correlation was found between the increment of C-peptide and duration of diabetes (r = -0.404, p less than 0.01). Our data show that residual B-cell function cannot be considered a protecting factor against the development of diabetic retinopathy.