The morphological base for the impaired function of the blood retinal barrier was studied in 50 eyes of 10 insulin dependent and 21 non-insulin dependent patients with various levels of diabetic retinopathy. The permeability of the blood retinal barrier (PBRB) was determined by vitreous fluorophotometry with correction for autofluorescence, lens transmission and non-protein bound plasma fluorescein concentration. Morphological abnormalities of diabetic retinopathy assessed by fundus photography and fluorescein angiography were individually scored on a decimal scale and related to the PBRB by multiple regression analysis. The PBRB was not correlated to morphological abnormalities of non-proliferative retinopathy [(1) microaneurysms, (2) hard exudates, (3) soft exudates, (4) intraretinal hemorrhages, (5) fluorescein leakage, and (6) capillary closure, p greater than 0.3]. The PBRB was correlated to morphological abnormalities of (pre)proliferative retinopathy [(1) intraretinal microvascular abnormalities (SIRMA) and (2) new vessels (Sneo): PBRB = A+B.SIRMA + C.Sneo with PBRB in nm/sec, A = 1.5 +/- 0.5, B = 0.9 +/- 0.2 and C = 1.7 +/- 0.4, R2 = 0.65, p less than 0.0001]. It can be concluded that the increased blood retinal barrier permeability in diabetic patients is mainly due to (pre)proliferative abnormalities and not to non-proliferative abnormalities.