Male Long-Evans rats were divided into four groups based on the concentrations of the AlF3 in the drinking water: 0.5 ppm, 5.0 ppm, 50 ppm, or a control solution of double-distilled, de-ionized water. Water was available ad libitum for 45 weeks. Following the behavioral studies, histological, immunohistochemical, and overall brain aluminum (Al) evaluations were made on portions of the brains from these animals. This report presents descriptions of the responses of the brains to the toxin exposure in regard to cell loss and other changes in the neocortex and hippocampus. The brain sections were immunohistochemically studied using antibodies both to neurofilament and phosphorylated neurofilament proteins. The three AlF3 groups did not differ from each other in overall brain Al content, but all treated groups had about twice the Al levels as did the control group. There were significant reductions in the number of neurons in the hippocampal CA1 and CA3 areas of the AlF3 treated groups. In addition the cells of the hippocampal formation appeared disorganized and many cells in all subdivisions stained excessively for Nissl-like proteins and that may reflect cellular dysfunction. Cells in the outer layers of the neocortex of the AlF3 groups exhibited darker Nissl staining and were more argentophilic than cells in similar areas from brains of the controls. These intracellular accumulations were not associated with increases in either phosphorylated or non-phosphorylated protein. There were large numbers of GFAP-positive cells in the brains of rats from all groups but the number of reactive cells was not greater in the treated animals than in the controls.