Alkaline secretion (AS) measured under basal conditions in oxyntic and antral pouches of conscious dogs averaged about 20 mumol/30 min and was about three times lower than that from the duodenal pouch. Natural prostaglandin E2 and prostaglandin F2 alpha, but not prostaglandin I2, were effective stimulants of AS, mainly when given topically. Stable analogues such as 16,16-dimethyl prostaglandin E2 and prostaglandin I2 were relatively more potent stimulants than their parent prostaglandins (PGs), particularly when applied topically. The highest alkaline response of the oxyntic pouch to PG was about 5% of the maximal acid response of this pouch to histamine. Indomethacin reduced markedly AS from the duodenal but not from the oxyntic or antral pouch. AS from the duodenal pouch was relatively more sensitive than that from gastric pouches to the stimulation by PGs, which were effective also after pretreatment with indomethacin. This study shows that the oxyntic, antral, and duodenal mucosa of conscious dogs is capable of secreting bicarbonate, and this secretion, particularly from the duodenal mucosa, is highly sensitive to the stimulation with certain PGs, mainly of the E and F type and their analogues, and to suppression by indomethacin, a potent inhibitor of PG biosynthesis, suggesting that endogenous PGs are involved in the mechanism of AS.