The influence of peripheral somatostatin immunoneutralization on intravenous (i.v.) and intracerebroventricular (ICV) bombesin-induced inhibition of gastric acid secretion (GAS) was investigated with the somatostatin monoclonal antibody, CURE.S6, in rats. The somatostatin antibody, injected i.v. in conscious rats with a chronic gastric fistula and i.v. catheter, did not modify basal GAS, whereas in urethane-anesthetized rats the basal GAS was increased by 150%. In conscious rats, somatostatin (15 micrograms/kg/h, i.v.) inhibited basal GAS by 50% after injection of control antibody but not after pretreatment with the somatostatin antibody. With pretreatment with a control antibody, bombesin (10 micrograms/kg/h, i.v.) inhibited basal GAS by 60% in conscious rats and by 50% the acid response to pentagastrin infusion in urethane-anesthetized rats. Bombesin injected ICV (3 and 10 ng/10 microliters/rat) inhibited basal GAS by 50% and 70%, respectively, in conscious rats pretreated with a control antibody. The somatostatin antibody injected i.v. before i.v. or ICV injection of bombesin did not influence bombesin-induced inhibition of GAS in conscious or anesthetized rats. These results show that peripheral somatostatin does not play a major role in the inhibition of gastric acid secretion induced either by ICV or i.v. administration of bombesin or basal acid secretion in conscious rats.