Vitreous fluorophotometry (VFP) using the Fluorotron Master was performed in 25 insulin-dependent diabetic patients with either minimal or no retinopathy and 22 controls. At 30 minutes, baseline corrected vitreous fluorescence values 3 mm from the retina were significantly greater in diabetic patients with minimal retinopathy than in either controls or patients with no retinopathy but were similar in patients with no retinopathy and controls. At 1 hour, vitreous fluorescence values and fluorescein permeability indexes were similar in all three groups. The absence of increased posterior vitreous fluorescein leakage in the diabetic patients with no retinopathy suggests that the alteration in permeability of the blood retinal barrier, as assessed by current VFP measures, does not precede the development of clinical diabetic retinopathy. However, the significantly increased 30-minute 3-mm fluorescence values suggest that posterior fluorescein leakage is increased in minimal background diabetic retinopathy.