The effect of two known inhibitors of prostaglandin synthesis, indomethacin and aspirin, on blood flow was studied in six Heidenhain pouch and three antral pouch dogs. The unstimulated gastric mucosa was bathed with 0.15 M HCl and clearance of [14C]-aminopyrine was used as an index of changes in mucosal blood flow. [14C]aminopyrine clearance was measured during three 15-min predrug periods and five 15 min-postdrug periods. Either indomethacin (10 mg . kg-1), aspirin (100 mg . kg-1), or 0.15 M NaCl were given intravenously as a bolus. Indomethacin reduced mucosal blood flow in the Heidenhain pouch 52% (P less than 0.05) and in the antral pouch 52% (P less than 0.05). Aspirin reduced Heidenhain pouch mucosal blood flow 31% (P less than 0.05). Indomethacin caused no significant change in electrical potential difference or in net flux of H+ or Na+ in Heidenhain pouches. Indomethacin (10 mg . kg-1 iv) produced no change in mean arterial pressure. We conclude that indomethacin and aspirin reduce unstimulated gastric mucosal blood flow, suggesting that endogenous prostaglandin may contribute to its maintenance.