Total retinal volumetric blood flow rate was measured in 12 normal subjects and 18 poorly controlled diabetic patients with background diabetic retinopathy. Maximum or center-line erythrocyte velocity (Vmax) was assessed by bidirectional laser Doppler velocimetry in four to five major retinal veins of one eye of each subject. Venous diameter (D) was measured from monochromatic fundus photographs. Total venous cross-section and measured total retinal volumetric blood flow in the diabetic patients were significantly larger than normal (P = 0.001 and P = 0.02, respectively). A positive linear correlation was found between Vmax and D in normal and diabetic eyes. Volumetric blood flow rate, Q, varied with D at a power of 2.87 in normal eyes. Total volumetric blood flow correlated with total venous cross-section. It was found that Q in the temporal retina was significantly larger than in the nasal retina in normal subjects (P = 0.0008) and diabetic patients (P = 0.0002). A significant difference in Q was observed between the superior and inferior retina in diabetic patients (P = 0.03) but not in normal subjects. The retinal vascular regulatory response to 100% oxygen breathing was reduced (P = 0.019) in diabetic patients and correlated with the level of background diabetic retinopathy. A close estimate of total volumetric blood flow may be obtained from blood flow measurement in one major retinal vein and the determination of total venous cross-section. This may be important for clinical studies in which measurements of all individual retinal veins may not be feasible.