In dogs provided with Heidenhain pouch and gastric fistula, we studied the effect of near-total excision of the fundic mucosa of the main stomach on acid secretion and gastrin release. Fundic mucosal excision abolished the mean response of the gastric fistula and reduced its maximal response to pentagastrin and to histamine by 85%. The basal Heidenhain pouch acid output increased ninefold, and fasting levels of serum gastrin increased from 36 +/- 3 pg/ml before the 248 +/- 47 pg/ml after fundic mucosa excision. The peak gastrin response to meal rose from 168 +/- 12 before to 392 +/- 49 pg/ml after. This increase could not have been due to changes in pH during the meal as meal pH was held constant at 5.5 by the method of intragastric titration in both pre- and postexcision studies. Following fundic mucosal excision, the acid response of the Heidenhain pouch to meal and to both submaximal and maximal doses of pentagastrin and histamine increased markedly. The maximal response to the meal increased from 41 +/- 9 before to 167 +/- 43 after, expressed as percent of the preexcision maximal histamine output. The corresponding changes in the maximal responses to pentagastrin respectively before to 124 +/ 26 and 230 +/- 31 after, again expressed as percent of the preexcision maximal histamine output. These observations suggest that fundic mucosal excision removes an inhibitory mechanism of both acid secretion and gastrin release.