In this study of the toxicokinetics of aluminum we have examined some of the fundamental issues that currently define our understanding of the toxicology of aluminum in humans. There is a vast literature on this subject, and it was not our aim to review this literature but to use it to develop our understanding of the toxicokinetics of aluminum and to identify critical and unresolved issues related to its toxicity. In undertaking this task we have chosen to define the term toxicokinetics to encompass those factors that influence both the lability of aluminum in a body and the sites at which aluminum is known to accumulate, with or without consequent biological effect. We have approached our objective from the classical pharmacological approach of ADME: the absorption, distribution, metabolism, and excretion of aluminum. This approach was successful in identifying several key deficits in our understanding of aluminum toxicokinetics. For example, we need to determine the mechanisms by which aluminum crosses epithelia, such as those of the gastrointestinal tract and the central nervous system, and how these mechanisms influence both the subsequent transport and fate of the absorbed aluminum and the concomitant nature and severity of the biological response to the accumulation of aluminum. Our hope in highlighting these unresolved issues (summarized in Table 1) is that they will be addressed in future research.