In Alzheimer's disease, it has been recognized that there is a dramatic tendency for the development of neurofibrillary tangles among neurons of cortical regions associated with the olfactory system. We have demonstrated that neurofibrillary tangle-bearing neurons contain dramatically elevated levels of aluminum. The olfactory system, the only portion of the central nervous system with exposure to the external environment, is uniquely capable of uptake and transneuronal spread of exogenous substances. We argue that inasmuch as aluminum is not employed in any physiologic process, these deposits must arise from exogenous sources. Using parkinsonism-dementia complex of Guam as a model, we present data which suggest that the olfactory system is particularly vulnerable to damage and is affected very early in the disease. This supports the concept that etiologic agents of importance to this epidemic may be airborne in nature and may enter the central nervous system via the olfactory pathways.