An in situ rat gut preparation was used to elucidate the mechanisms of gastrointestinal aluminum (Al) absorption. Al uptake rate at the mucosal surface was decreased by the paracellular pathway blockers kinetin (1 mM) and 2,4,6-triaminopyrimidinium (10 mM), by sodium removal with choline substitution and by treatment with amiloride (1 mM), an epithelial sodium transport blocker. The rate of Al uptake was unchanged by 2,4-dinitrophenol (0.1 mM), 4-aminopyridine (0.1 mM, 0.5 mM) and verapamil (0.1 mM). The rate of Al uptake was increased from a medium containing no added calcium, a treatment which decreases resistance to flux in the paracellular pathway. These results suggest that gastrointestinal Al uptake occurs by an energy-independent, sodium-dependent, paracellular pathway-mediated process.