The antisecretory and antiulcer effects of diphenyl diselenide were studied in vivo and in vitro. Diphenyl diselenide, administered intraperitoneally prevented the development of gastric lesions induced by ethanol and indomethacin. There was no difference in plasma uric acid concentrations in diphenyl diselenide-treated rats with gastric lesions induced by 70% ethanol. There were no changes in TBARS levels in diphenyl diselenide-treated rats with gastric lesions induced by indomethacin and ethanol. Diphenyl diselenide (5, 10 and 50mg/kg) inhibited gastric acid secretion in pylorus-ligated rats. In vitro results demonstrated that diphenyl diselenide inhibited lipid peroxidation induced by Fe(2+)/ascorbate/H(2)O(2) and reduced K(+)-dependent ATPase activity. The mechanisms by which pre-administered diselenide protects the damaged area in the gastric mucosa are not clear but it appears that the antiulcer activity of diphenyl diselenide is the result of antisecretory activity, via inhibition of gastric K(+)-ATPase activity.