Pancreatic secretions were collected during endoscopic retrograde cholangiopancreatography from 15 subjects without pancreatic, biliary, or hepatic diseases, 11 patients with non-insulin-dependent diabetes, and 11 patients with insulin-dependent diabetes. Pancreatic secretion was stimulated by the intravenous administration of one unit of secretin per kilogram of body weight. Immunoreactive somatostatin (IRS) in the pancreatic juice of the nondiabetic subjects ranged from 43 to 97 pg/ml, in non-insulin-dependent diabetics from 5 to 3872, and in the insulin-dependent diabetics from 0 to 2093. IRS in insulin-dependent diabetics under good plasma glucose control ranged from 0 to 281 pg/ml, compared to those under poor control who ranged from 518 to 2093 pg/ml. These results indicate that IRS in pancreatic juice is higher in poorly controlled insulin-dependent diabetics than in well controlled insulin-dependent diabetics and nondiabetics. Whether these changes in IRS are purely secondary phenomena or play some pathogenetic role in the disturbed metabolism of diabetes remains to be proven. The chromatographic profile of IRS in pancreatic juice on both gel filtration and high-performance liquid chromatography has indicated that these IRS moieties represent somatostatin 14 and somatostatin 28.