We studied the secretion of somatostatin and HCl and the release of vasoactive intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP) from isolated, vascularly perfused, porcine non-antral stomach. Electric vagus stimulation increased acid secretion and the release of VIP and GRP and inhibited somatostatin secretion as determined in the venous effluent. Atropine abolished the HCl response and reversed the somatostatin inhibition to a three-fold increase, whereas GRP and VIP responses were unchanged. Both intra-arterial carbachol (10(-6) M) and GRP (10(-8) M) increased acid secretion and inhibited somatostatin secretion. VIP (10(-8) M) increased somatostatin secretion and had no effect on acid secretion. By immunohistochemistry, somatostatin was localized to both open-type and closed-type cells equally spread in the various parts of the gastric glands without particular relation to the parietal cells. Numerous GRP- and VIP-immunoreactive nerve fibers were seen between the glands. It is concluded that the fundic and antral secretion of somatostatin, investigated in a previous study, are differently regulated. The relation of fundic somatostatin release to acid secretion seems to be complex.