Intramural neurons in the fundus of the isolated mouse stomach were activated by 1,1-dimethyl-4-phenylpiperazinium (DMPP) or by electrical field stimulation and the participation of cholinergic and bombesin/gastrin-releasing peptide (GRP) neurons in the regulation of acid secretion evaluated with atropine and a selective bombesin/GRP antagonist, [Leu13-psi(CH2NH)-Leu14]bombesin. For both DMPP and field stimulation, atropine inhibited acid secretion and augmented somatostatin secretion. The bombesin/GRP antagonist had an opposite effect, augmenting acid secretion and inhibiting somatostatin secretion to below basal levels. The combination of the two antagonists restored DMPP- and field-stimulated acid and somatostatin secretion to basal levels. The results indicate that neurally stimulated acid secretion in the isolated mouse stomach is regulated by cholinergic neurons that mediate stimulation and bombesin/GRP neurons that mediate inhibition of acid secretion. Cholinergic neurons exert their stimulatory effect by acting directly on parietal cells and indirectly by eliminating the inhibitory influence of somatostatin. Bombesin/GRP neurons exert their inhibitory effect mainly by inducing release of somatostatin; an additional direct inhibitory effect of bombesin/GRP neurons on parietal cells is possible.