Blood-brain barrier (BBB) permeability to 24Na+, 36Cl-, and [3H]sucrose was studied in rats after 2 wk of streptozocin-induced diabetes. The PS (permeability-surface area product) for Na+ in the cortex of the frontal lobes was 5.4 +/- 0.6 (10(-5) cm3 X g-1 X s-1; +/- SD) in diabetic rats compared with 7.1 +/- 1.7 in control rats. In the occipital cortex, the values were 7.6 +/- 1.5 and 9.9 +/- 1.6, respectively. In contrast, BBB permeability to Cl- and sucrose remained unchanged. We conclude that a selective alteration in BBB permeability to Na+ unrelated to changes in brain capillary surface area is present in experimental diabetes.