Previously, we demonstrated that both antacids and sucralfate can protect the gastric mucosa against alcohol injury. Since these compounds contain aluminum, we studied whether other aluminum compounds have cytoprotective properties as well. Fasted rats were pretreated intragastrically with A) 0.9% NaCl, B) sucralfate, C) aluminum-magnesium antacid gel, D) Al2(SO4)3, E) Al(OH)3, and 1 h later they received 2 ml 100% ethanol by gavage. The stomach was removed and assessed for injury 3 h after ethanol administration. Control (group A) rats had 39 +/- 3% gross mucosal injury, which was reduced to 5 +/- 1% with sucralfate, 7 +/- 1% with Al2(SO4)3, 12 +/- 2% with Al(OH)3, and 16 +/- 2% with aluminum-magnesium antacid gel pretreatment. Microscopic surface epithelial injury and submucosal edema were seen in all five groups, while deep mucosal necrosis was largely prevented by pretreatment in groups B to E. These findings indicate that aluminum in a wide variety of molecular forms can protect the gastric mucosa against alcohol injury.