SUMMARY Background: Gastric antisecretory agents may inhibit the synthesis or secretion of gastric mucin during acid suppression, which would interfere with mucosal protection and limit the efficacy of the agents. Methods: Rats were dosed with famotidine, omeprazole, or buffer control for 4 weeks. Mucin synthesis, mucin histochemistry, mucin carbohydrate composition and prostaglandin E, (PGE,) release were measured during and after drug treatment. Results : PGE, release was maximally inhibited after 2 weeks of omeprazole or 4 weeks of famotidine. Total glycoprotein synthesis was inhibited at all times by omeprazole, but only after the cessation of dosing with famotidine. Sulphated glycoprotein synthesis was inhibited by both drugs at 2 weeks. PGE,release and sulphated glycoprotein synthesis were restored to control values or more by the 5th day after the end of dosing, at which time total glycoprotein synthesis was significantly suppressed in both groups. Histologically, a reduction of PAS-positive surface mucus was observed after 2 weeks of dosing in both groups. Both famotidine and omeprazole reduced the sialic acid content during and after treatment. Conclusions : These results suggest that Iong-term antisecretory therapy also affects the production of factors involved in primary gastric mucosal defence, which should be considered in the assessment of response to treatment in clinical trials.