The effects of a 210 min infusion of 1.8 nmol/kg somatostatin-14 (SS-14), somatostatin-28 (SS-28), and vehicle (Haemaccel) alone, on arginine- and insulin-stimulated release of pancreatic hormones were tested in 5 normal male subjects. Arginine administered at 30-60 min induced an increase in plasma glucose concentrations which was enhanced by SS-14 and further increased by SS-28. SS-28 was more effective than SS-14 in suppressing the arginine-induced secretion of insulin. Arginine-stimulated and insulin-stimulated (at 120 min) glucagon release was equally suppressed by SS-14 and SS-28, as was insulin-stimulated pancreatic polypeptide secretion. At the end of the SS-14 infusion the mean plasma somatostatin level was approximately 28% of that which occurred during the SS-28 infusion. The results are discussed in relation to similar studies in vitro and in vivo in laboratory animals and to a possible role of the two forms of SS in carbohydrate homeostasis.