Vitreous fluorophotometry was carried out in 99 juvenile-onset, insulin-dependent diabetics and 31 control subjects. The mean vitreous fluorescein concentration one hour after intravenous administration of fluorescein, 7 mg/kg, was 5.4 +/- 0.3 ng/ml (mean +/- SEM) for controls and 9.5 +/- 0.4 ng/ml for diabetics (P less than .005). Diabetic patients with or without background retinopathy, when randomly matched for age or duration of their disease, had similar vitreous fluorophotometry measurements. The break-down of the blood-retinal barrier to fluorescein appears to be the earliest detectable ocular abnormality of diabetes.