Studies were designed to establish the acid inhibitory potency and plasma kinetics of somatostatin-28 (S-28) in humans and to determine whether the amount of S-28 released into the circulation after a meal is sufficient to regulate gastric acid secretion. A liquid meal induced a significant increase of S-28 (P < 0.01) whereas S-14 levels did not change. Postprandial S-28 concentrations were then mimicked by exogenous infusions and tested on basal and pentagastrin-stimulated gastric acid secretion. Expressed in terms of circulating plasma concentrations measured by specific radioimmunoassays, S-14 was 10 times more potent than S-28 in inhibiting gastric acid production. The plasma half-life of S-28 (1.86 min) was longer than that of S-14 (1.00 min) due to a slower plasma clearance rate. S-28 did neither affect basal and stimulated gastric acid secretion nor postprandial intragastric acidity. These studies suggest that postprandial plasma concentrations of S-28 are unlikely to regulate gastric acid secretion in man. They also show that S-28 is several times less potent than S-14 with respect to inhibition of gastric acid output.