The consequences of renal functional impairment on aluminum (Al) excretion are not clear inasmuch as little is known about its glomerular filtration, tubular reabsorption, or secretion. The association of Al and the etiology of the dialysis encephalopathy syndrome and osteomalacia among patients with uremia suggests that renal functional impairment is a prerequisite for increased body Al stores. However, considerable evidence argues against the concept that tissue Al accumulation occurs as a simple consequence of renal failure. Many dialysis patients have high parathyroid hormone (PTH) concentrations that have been associated with neurologic abnormalities, bone disease, and anemia. The toxicity of PTH could be either direct or indirect by influencing the metabolism of potentially toxic substances such as Al. Our studies in normal rats suggest that gastrointestinal Al absorption and specific tissue burdens are enhanced by PTH, but not irreversibly, because the withdrawal of PTH resulted in Al egress. Dialysis patients are often treated with vitamin D analogs to prevent or control consequences of hyperparathyroidism and impaired 1,25-dihydroxycholecalciferol synthesis. Although some reports suggest that high bone Al in osteomalacia may be responsible for vitamin D resistance, our studies with normal rats suggest that its metabolites may also increase tissue Al burdens independent of PTH action. Thus, several factors operative in uremia other than impaired renal function may contribute to altered Al metabolism and, consequently, to its toxicity.