Sixteen healthy male volunteers participated in a randomized, double blind, parallel groups study. Subjects received either 1 or 5 mg SDZ CO 611 (a new, orally active somatostatin analog) twice daily over a 14-day period and acted as their own controls. Gastric emptying of 99mTc and mouth to cecum transit time, as measured by the breath hydrogen technique, after a mixed meal containing lactulose and 99mTc-diethylenetriaminepentaacetate, were assessed once before, twice during, and once after the period of study medication. Gastric emptying of 99mTc was significantly accelerated by the higher dose of SDZ CO 611, whereas mouth to cecum transit time was prolonged by the drug in a dose-dependent manner. Both doses of SDZ CO 611 led to suppression of the fasting level and postprandial release of several gastrointestinal and pancreatic hormones. This effect was more marked in those subjects taking 10 mg/day of the study medication. Motilin and pancreatic polypeptide were the most sensitive to the inhibitory actions of the analog. Glucose tolerance was significantly impaired by the 10-mg dose of the drug. We conclude that this new, orally active derivative of somatostatin is as effective on the gastrointestinal tract as the sc somatostatin analog octreotide. It would, therefore, be a useful advance in the treatment of gastroenteropancreatic tumors.