To examine the effect of Helicobacter pylori lipopolysaccharide on gastric secretion, the present study was carried out using pylorus ligated conscious rats. Intraperitoneal administration of Helicobacter pylori lipopolysaccharide significantly inhibited gastric acid secretion (4 hr) in a dose-dependent manner (0.033-1.0 mg/rat). The Helicobacter pylori lipopolysaccharide (1 mg/rat)-induced acid inhibition was still observed 8 hr after injection. Gastric acid secretion (4 hr) was compared in the rats that had received intraperitoneal administration of 1 mg/rat dose of Helicobacter pylori lipopolysaccharide or saline alone 24 hr before. There was no significant difference in gastric acid secretion between the saline- and H. pylori lipopolysaccharide-treated rats. These results suggest for the first time that H. pylori lipopolysaccharide may inhibit acid production, and this acid inhibition may be long-lasting. It is also demonstrated that this anti-secretory action of H. pylori lipopolysaccharide has a reversible effect on gastric secretion. All these results suggest that H. pylori lipopolysaccharide might be involved in the low acid secretory function seen in patients with acute H. pylori infection.