This study was designed to determine the involvement of nitric oxide (NO) in gastric and duodenal alkaline under basal conditions and in response to exogenous and endogenous stimulants in conscious dogs with Heidenhain pouches and duodenal loops. A topical application of HCl or capsaicin increased both gastric and duodenal alkaline secretion. A meat meal stimulated only duodenal alkaline secretion while gastric secretion was not significantly changed. The NO synthase inhibitor, NG-nitro-L-arginine (L-NNA), significantly inhibited basal gastroduodenal alkaline secretion and almost completely suppressed the alkaline responses to food, acid or capsaicin. L-arginine given alone did not affect significantly basal or stimulated gastroduodenal alkaline secretion but when given together with L-NNA partially reversed the inhibitory effects of L-NNA on this secretion. For the comparison, the administration of indomethacin to suppress the generation of prostaglandin biosynthesis, also reduced basal and stimulated alkaline secretion but this reduction was relatively smaller than that attained by the inhibition of NO synthase with L-NNA. Luminal application of nocloprost, a stable prostaglandin E2 analog, and glycerin trinitrate caused significant increase in both gastric and duodenal alkaline secretion but these responses were not affected by the administration of L-NNA or indomethacin. We conclude that endogenous NO together with prostaglandins plays a significant role in secretory alkaline response of gastroduodenal mucosa to acid, food and capsaicin.