Hange-shashin-to (HST) is a traditional Chinese herbal prescription (Banxia Xiexin Tang) which has long been used in the therapy of gastric functional disorders. In this report, the effect of HST extract on water-immersion restraint stress-induced gastric ulcer based on the changes in gastric mucin content and the variations of monoamine contents in hypothalamus were investigated. Ulcer index was microscopically measured by the sum total of the lengths of ulcers in glandular stomach. Gastric mucin content was determined by a PAS-staining methods and the monoamine contents were detected by HPLC-ECD method. HST extract was orally administered at 1, 2 and 3 g/kg for three consecutive days before stress exposure. Water-immersion restraint stress decreased the mucin content and produced gastric ulcers in a restraint time-dependent manner. Pretreatment with HST extract markedly inhibited the reduction of gastric mucin content and the development of gastric ulcer with significant differences (p < or = 0.01). The remarkable decrease of NE and 5-HT contents but prominent increases of MHPG and 5-HIAA contents were observed in hypothalamus after water-immersion restraint stress (p < or = 0.01). Those changes in monoamine contests in hypothalamus were also significantly inhibited by the pretreatment with HST extract at higher dosage (p < or = 0.05). These results indicate that the changes in gastric mucin content and the variation of monoamines in hypothalamus relate to the pathogenesis of water-immersion restraint stress-induced gastric ulcers, and it is suggested that the prophylactic effects of HST extract on stress induced gastric ulcers may be associated with an increase in gastric mucin content, although the prevention of HST extract on the extraordinary changes in monoamine contents in hypothalamus due to stress cannot be ruled out.