Neurotoxic effects of aluminum (AI) were recognized >100 years ago, but have only recently been studied in detail. By far, the most dramatic effect of Al is that of producing intraneuronal perikaryal neurofilamentous aggregates, which consist of phosphorylated neurofilaments. Several species have been used to demonstrate this effect, rabbit being most common; the effect also is seen in in vitro systems. Besides its role in producing neurofibrillary pathology, Al appears to modify the blood-brain barrier and exert cholinergic and noradrenergic effects. Possible mechanisms of Al neurotoxicity could be related to cell damage via free radical production, impairment of glucose metabolism, and effects on signal transduction.