The integrity of the blood-retinal and blood-glomerular vascular barriers were investigated simultaneously in diabetic individuals to determine whether or not the early forms of diabetic retinopathy and nephropathy are temporally related. The blood-retinal barrier was assessed by the technique of vitreous fluorophotometry. Twenty-four hour urinary excretion of albumin was determined by radioimmunoassay before fluorescein measurement. Posterior vitreous fluorescein leakage was greater in the study cohort than in the control population after diabetes had been present 11-20 years (p < 0.05) and 21 years or more (p < 0.01). Albumin excretion was also increased in the diabetic subjects (p < 0.001) and correlated to duration of diabetes (r = 0.51, p < 0.005). Hypertension raised midvitreous fluorescein levels (p < 0.05), but it had no effect on posterior vitreous values. Hypertension was an independent predictive factor for urinary albumin excretion (p < 0.05). Partial correlation analysis showed that vitreous fluorescence and urinary protein were not significantly correlated when controlled for duration of diabetes and for age. Early proteinuria did not predict retinal vascular leakage, nor did increased fluorescein leakage predict renal decompensation in the diabetic subjects. The data suggest that during the early stages of retinal and renal abnormalities associated with insulin-dependent diabetes, the eye and kidney follow different temporal courses to abnormal function.