In previous work we have demonstrated that dehydroleucodine (DhL) prevents gastric damage induced by necrosis-inducing agents such as absolute ethanol (EtOH). In this study we examine the effects of DhL on gastroduodenal morphology and monoamine levels by histological and biochemical methods, respectively, as an approach to elucidating the cytoprotective mechanism of the drug. Histological evidence shows that DhL prevents formation of gastroduodenal mucosal lesions induced by EtOH and that this protective effect is related to the ability of the drug to stimulate mucus production. DhL itself does not affect the tissue concentration of NE, DA and 5-HT. However, it prevents the depletion of DA and 5-HT provoked by EtOH. We propose that the abundant mucoid blanket secreted after treatment with DhL acts as a diffusion barrier against EtOH. It is also possible that DhL could act as a "cell stabilizer," by inhibiting the degranulation of cells containing monoamines.