Abnormalities in ocular fluorophotometry occur in human and experimental diabetes mellitus. To determine the reversibility of these abnormalities, we studied prospectively 11 intensively treated and 25 conventionally treated insulin-dependent diabetics (IDD) preselected because of abnormal vitreous fluorophotometry. Among the 25 IDD treated conventionally with one or two insulin injections daily, hemoglobin A1C concentrations remained elevated and fluorescein concentration, 1 h after the intravenous injection of fluorescein (7 mg/kg), did not change significantly in either the anterior chamber or the posterior vitreous. Among 11 IDD treated intensively with home blood glucose monitoring and pumped subcutaneous insulin or three or more injections daily, hemoglobin A1C fell dramatically (10.4 +/- 0.7% to 7.5 +/- 0.2%) and anterior chamber fluorescein concentration decreased (73.9 +/- 7.7 to 49.5 +/- 5.3 ng/ml). Two patients with proliferative retinopathy showed no improvement in their massive vitreous fluorescein accumulation and subsequently required photocoagulation. In the nine subjects without proliferative retinopathy, vitreous fluorescein accumulation decreased in eight (10.6 +/- 0.7 to 6.5 +/- 0.5 ng/ml) and was normal in six after 1 yr. The only subject with increasing vitreous fluorescein accumulation also had concurrent worsening of background retinopathy. These studies support the hypothesis that moderate abnormalities in ocular fluorophotometry are due to reversible changes in ocular tissues, such as retinal pigment epithelium. Fluorescein leakage emanating from the advanced vascular or retinal abnormalities of proliferative retinopathy were not reversed with the degree and duration of metabolic control achieved in the present study. The long-term significance of the reversal of moderate abnormalities in fluorophotometry is not clear at the present time.