Vitreous fluorophotometry is a new quantitative method for evaluation of the blood-retinal barrier (BRB). The application of this method to a series of diabetic patients with apparently normal fundi revealed the presence of a significant breakdown of the BRB in the early stages of retinal involvement in diabetes. This alteration of the BRB appears to be the earliest clinically detectable change to occur in the retina in diabetes. Higher vitreous fluorophotometry values, indicating a more marked breakdown of the BRB, occurred in patients who were under worse metabolic control. Higher vitreous fluorophotometry values were also associated with the development of visible retinal lesions.