To get better insights into the pathological and biochemical defects underlying aluminum toxicity in brain tissue, we exposed male albino rats for 35 days to aluminum sulfate by gavage. Tissue aluminum level of brain was assessed, histological sections of brain were examined and amino acid transmitters contents were detected by reversed phase high performance liquid chromatography. Aluminum levels were high in brain specimens of the treated groups comparing to the control and it was dose-dependent. Marked increase in glutamate and glutamine levels was noticed while GABA level was significantly decreased. The most pronounced changes in brain tissue included spongioform changes in the neurons specially those of hippocampus, nuclear deformity, and neurofibrillary degeneration, similar to neurofibrillary tangles in Alzheimer's disease. It is concluded that accumulated aluminum in brain and altered amino acid neurotransmitters are important mechanisms of aluminum neurotoxicity.