The new long-acting somatostatin analogue octreotide (SMS 201-995) was investigated for its influence on secretagogue-stimulated human exocrine pancreatic secretion. Eighteen healthy volunteers participated in the study. During duodenal intubation with a background stimulation of either secretin 1 U.kg/h or secretin 1 U.kg/h + ceruletide, 120 ng.kg/h, octreotide was infused at doses of 5, 20 and 80 micrograms/h in a placebo-controlled randomized double-blind crossover trial. Duodenal juice samples were collected in 10-min intervals, and amylase, trypsin, chymotrypsin, and bicarbonate were measured in the individual fractions. During secretin stimulation, amylase was inhibited between 41 and 59%, trypsin between 28 and 72%, chymotrypsin between 55 and 70%, and bicarbonate between 0 and 31% with 5, 20 and 80 micrograms/h octreotide. During secretin and ceruletide stimulation, amylase was significantly inhibited by 84%, 78%, 81%, trypsin by 76%, 55%, 52%, chymotrypsin by 77%, 55%, 60%, and bicarbonate by 25%, 11%, 19% with 5, 20, and 80 micrograms/h octreotide, respectively (all decreases P less than 0.05). The long-acting somatostatin analogue octreotide was confirmed to be a potent inhibitor of stimulated human exocrine pancreatic secretion. The near maximal inhibitory potency of octreotide was achieved at a dose of only 5 micrograms/h. This finding may be of value in the planning of therapeutic studies with octreotide.