To determine whether aluminum alters the permeability of the blood-brain barrier (BBB), 4 groups of rats were given an intraperitoneal injection of aluminum chloride, aluminum lactate, aluminum hydroxide or physiological saline. Two hours later, [14C]sucrose was injected, and brain radioactivity was measured from 5 different brain regions. The permeability capillary surface area (PA) was calculated by the dual compartment model (plasma-brain) proposed by Rapoport et al. The PAs for [14C]sucrose were significantly elevated in all brain regions of the animals injected with the aluminum chloride or aluminum lactate. However, the aluminum hydroxide group showed no BBB permeability change. In the second experiment, the reversibility of the aluminum induced BBB change was examined. PA was determined at 2, 4 or 24 h after exposure to aluminum lactate. Significant permeability changes were observed at 2 and 4 h after aluminum. However, the difference disappeared by 24 h. These findings indicate that exposure to a high level of aluminum alters the function of BBB in the rat and the aluminum induced BBB change is reversible. An increase in the blood aluminum level and time after exposure appear to be important factors associated with the BBB permeability change. Implications of the results are discussed in terms of aluminum's potential action on the endothelial cells.