Pancreatic reaction after endoscopic papillosphincterotomy (EPT) is a common event occurring in about 70% of cases. Acute pancreatitis may also develop in 1%-6% of cases. Previous attempts to prevent this reaction with an inhibitor of exocrine pancreatic secretion such as somatostatin provided conflicting results. The somatostatin long-acting analogue octreotide has recently proposed for the prevention of ERCP/EPT-induced pancreatic reaction. Therefore we tested the prophylactic effect of a subcutaneous administration of octreotide in two different dosages in 60 consecutive patients undergoing EPT for common bile duct stones and benign papillary stenosis. They were given either octreotide 0.2 mg (20 cases), or octreotide 0.1 mg (20 cases), or placebo (20 cases) before the procedure. Serum amylase levels were determined at baseline and 2, 4, 8 and 24 hours thereafter. The differences were statistically significant at 2 hours between subjects pretreated with octreotide 0.2 mg and control subjects (p = 0.01); at 4 and 8 hours after the procedure between both octreotide-treated groups and control subjects (octreotide 0.1 mg: p < 0.05, at 4 and 8 hrs; octreotide 0.2 mg: p = 0.01, at 4 hrs, and p < 0.01, at 8 hrs). In patients with previous episodes of relapsing pancreatitis, the increase in serum amylase was significantly reduced in the octreotide 0.2 mg group vs control group, at 4 hrs (p < 0.05) and 8 hrs (p < 0.05). Our data suggest that octreotide 0.2 mg has a greater prophylactic efficacy than 0.1 mg in reducing pancreatic reaction after EPT.