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The gastric exocrine inhibitory activities of somatostatin-28 (SS-28) and somatostatin-14 (SS-14) were determined in conscious cats prepared with gastric fistulae. Gastric acid and pepsin secretions were stimulated with pentagastrin. Expressed in terms of exogenous doses, SS-14 (ID
50: 1.49 nmol · kg
−1 · h
−1) was 3.4 times more potent than SS-28 (ID
50: 5.12 nmol · kg
−1 · h
−1) as an inhibitor of gastric acid secretion. Similarly SS-14 (ID
50: 0.25 nmol · kg
−1 · h
−1) was 3.8 times more potent than SS-28 (ID
50: 0.96 nmol · kg
−1 · h
−1) as an inhibitor of pepsin secretion. Expressed in terms of circulating plasma concentration measured by radioimmunoassay, SS-14 (ID
50: H
+, 232 and pepsin 73 pM) was 8–9 times more potent than SS-28 (ID
50: H
+, 2112 and pepsin, 611 pM) as an inhibitor of gastric exocrine secretions. The plasma immunoreactive half-life of SS-28 (6.1 min) was double that for SS-14 (2.4 min) possibly due to a slower theoretical metabolic clearance rate of the larger peptide (30 and 87 ml · kg
−1 · min
−1, respectively). Both peptides had similar apparent distribution volumes (SS-14, 306 and SS-28, 263 ml · kg
−1). As judged by gel chromatography of plasma samples, there was no evidence for the conversion of SS-28 to SS-14 in vivo. The reduced activity of SS-28, compared with SS-14, against gastric exocrine secretions contrasts with its more potent effects in the pituitary and pancreas.