Aluminum has become a dietary toxin in modem times but its mechanism o
f absorption is poorly understood. After ingestion, the systemic trans
fer of aluminum is small but it is greatly affected by the coingestion
of certain dietary agents, such as citrate, that complex with the met
al in the intestinal lumen or transiently alter the permeability of th
e mucosa. Here, mechanisms of aluminum absorption were studied by usin
g freshly prepared aluminum hydroxide and aluminum citrate. Everted sa
cs of rat gut were used to investigate the site of absorption, effect
of chemical charge on absorption of aluminum citrate, and presence of
active or passive absorption with use of the metabolic inhibitor ouaba
in. Absorption was biphasic with a large tissue uptake that was consis
tent with adhesion to mucus-mucosal surface but little tissue transpor
t, which was consistent with passive paracellular permeation. Citrate
reduced the uptake-transport ratio both by competing with the mucosal
uptake and by increasing mucus-mucosal permeation but not by affecting
the charge of the luminal aluminum species. Despite the potential for
hydroxypolymerization of aluminum at intestinal pH, the small bowel a
nd colon absorbed aluminum passively and paracellularly but the stomac
h did not. The predominantly proximal absorption of aluminum observed
in vivo is a reflection of the proximal absorption, and therefore remo
val, of dietary constituents (eg, citrate) that enhance mucosal permea
tion of aluminum. The colon should be investigated further as a site o
f significant paracellular permeability.