A series of 77 patients with overt diabetes and with apparently normal fundi on ophthalmoscopy and fluorescein angiography was examined by vitreous fluorophotometry. Breakdown of the blood-retinal barrier, which appears to be the earliest clinically detectable change in the retina in diabetes, was a constant finding. Quantitative measurement by vitreous fluorophotometry of the breakdown of the blood-retinal barrier could be correlated with degree of metabolic control and previous duration of diabetic disease. Significantly higher vitreous fluorophotometry values, indicating a more marked breakdown of the bloodretinal barrier, were recorded in patients under poor metabolic control than in patients whose diabetes was under relatively better control. Similarly, patients who had had diabetes for longer periods of time showed higher vitreous fluorophotometry values than those recorded in patients with diabetes of shorter duration.