The uptake-index technique was used to study the effect of streptozotocin-induced diabetes on transport through the blood-retinal (BRB) and blood-brain barriers (BBB) in rats. Untreated diabetes reduced retinal and cerebral uptake of glucose but had no effect on the uptake of L-leucine. A similar reduction in glucose uptake was achieved by an intravenous infusion of glucose in normal rats. Insulin given 1-4 h before the experiments to diabetic rats normalized both blood-glucose levels and retinal and cerebral glucose uptake in diabetic rats. Experiments in hyperglycemic, normal rats suggested that both the preceding plasma glucose level and the concentration of glucose in the injected bolus influence retinal and cerebral uptake of glucose, and we conclude that competitive inhibition may explain the reduction in glucose uptake observed in untreated diabetes.