A~bstract. These studies were performed to assess the contribution of the pancreas to the somatostatinlike immunoreactivity (SLI) circulating in arterial and portal venous plasma. Basal SLI concentrations in arterial, pancreatic venous, and portal venous plasma were 95±9, 277±32, and 130±12 pg/mi, (+±SEM), respectively. Measurement of pancreatic and portal venous blood flow (5±1 vs. 365±46 ml/min) and hematocrit allowed calculation of net, base-line SLI output from the right lobe of the pancreas (521±104 pg/min) and from the gastrointestinal tract (8,088±1,487 pg/min), which suggested that the contribution of the pancreas to circulating SLI was minor when the D cells were not stimulated. To stimulate the secretion of SLI from both pancreatic and nonpancreatic sources, isoproterenol, a beta-adrenergic agonist, was infused intravenously for 1 h into six anesthetized dogs. Arterial SLI increased by 52±9 pg/ml; superior pancreatico-duodenal venous SLI increased by 380±95 pg/ml; portal venous SLI increased by 134±14 pg/ml. Pancreatic venous blood flow remained unchanged at 5±1 ml/min, but portal venous blood flow increased to 522±62 ml/min. SLI Volume 73, January 1984, 216-223 organ blood flow, can give a false impression ofthe organ's contributions of circulating SLI. To verify that the contribution of the pancreas was negligible, six dogs received an acute pancreatectomy and then an intravenous infusion of isoproterenol at the same rate. In these dogs, both the base-line level of SLI in arterial plasma (109±12 pg/ml) and the increment during isoproterenol (56±8 pg/ ml) were similar to those of normal dogs. Likewise, in pancreatectomized dogs both the base-line level of SLI in portal venous plasma (129±16 pg/ml) and the increment during isoproterenol (174±34 pg/ml) were similar to those of normal dogs. We conclude that, in normal dogs, the pancreas makes a negligible contribution to the basal and stimulated level of SLI in arterial and portal venous plasma and therefore that these levels should not be used as an index of secretory activity of the pancreatic D cells.