Antacids containing aluminum have been shown to stimulate the protective processes in the gastric mucosa and to enhance the healing of chronic gastroduodenal ulcerations, but the mechanisms of these effects are still unexplained. This study was designed to compare the protective effects of unmodified and acidified (pH 2.0) Maalox 70 and Al(OH)3 on the formation of acute gastric mucosal lesions induced by absolute ethanol, taurocholate, acidified aspirin and stress, and to determine the role of gastric acid in healing of chronic gastroduodenal ulcerations by these antacids in rats. Acidified Maalox 70 and Al(OH)3 were significantly more potent than unmodified agents against all four tested types of acute mucosal lesions, and this action was probably due to their ‘mild irritant’ effect as evidenced by extensive exfoliation of the surface epithelial cells observed microscopically after the exposure of the mucosa to these agents. Mucosal generation of prostaglandins does not appear to be involved in the gastroprotection by acidified Maalox because the pretreatment with indomethacin did not affect this protection. In contrast to the protective effect, the ulcer-healing capacity of Maalox or Al(OH)3 does not appear to be dependent upon the presence of gastric acid because the reduction or elimination of endogenous acid by the pretreatment with ranitidine or omeprazole did not affect the healing of gastroduodenal ulcerations. We conclude that aluminum-containing antacids induce the mucosal protection that is enhanced in the presence of luminal acid but exhibit an ulcer-healing property that appears to be unrelated to gastric acid secretion or mucosal generation of prostagland