The perfused rat stomach was used to investigate the effect of intragastrically administered somatostatin (S-14) on basal and pentagastrin-stimulated gastric acid secretion. Intravenous injection of pentagastrin (10 micrograms/kg body wt) induced a peak acid output (PAO) of 6.3 +/- 0.45 mu eq H+. With luminal perfusion of the stomach by S-14 (100 micrograms X kg-1 X min-1), no significant inhibition of gastric acid secretion was observed (PAO: 5.9 +/- 0.6 mu eq H+). The same dose of S-14 administered intravenously significantly inhibited acid secretion (PAO: 1.7 +/- 0.4 mu eq H+) as did intravenous injection of neutralized S-14-containing gastric perfusate obtained by perfusion from a different rat stomach (PAO: 1.9 +/- 0.5 mu eq H+). Intravenous injection of a saline gastric perfusate containing no S-14 did not alter gastric acid secretion (PAO: 6.3 +/- 0.7 mu eq H+). It is concluded that S-14 does inhibit gastric acid secretion when administered systemically but not by intraluminal application.