The activity of the novel proton pump with inhibitor lansoprazole was examined in different gastric secretion models in vitro and in vivo, in comparison with omeprazole. 2. In the conscious cat with gastric fistula lansoprazole (0.25-2 mumol/kg i.v.) caused a dose-dependent reduction of the acid secretion induced by dimaprit, pentagastrin, 2-deoxy-D-glucose and bombesin, being approximately as potent as omeprazole (0.25-1.5 mumol/kg i.v.). Similar to omeprazole, lansoprazole was also more effective when administered in hyperacidic states. 3. In the anaesthetized rat with lumen perfused stomach lansoprazole (0.03-1 mumol/kg i.v.) was approximately 3 times more potent than omeprazole (0.1-3 mumol/kg i.v.) in inhibiting the acid secretion induced by histamine, 2-deoxy-D-glucose and forskolin. 4. In the isolated gastric fundus from the immature rat lansoprazole (1-30 microM) reduced basal acid secretion and the acid response to histamine and forskolin, with a potency not significantly different from that of omeprazole. 5. No significant differences were found in the different species between lansoprazole and omeprazole as for the duration of action. 6. In conclusion, lansoprazole exerts a marked antisecretory effect in a variety of gastric secretion models from different species. However, it did not significantly differ from omeprazole when considering either the potency or the duration of action.