Nasogastric suction, glucagon, and cimetidine are proposed treatments for human acute pancreatic because they may reduce gastric acid and exocrine pancreatic secretion. However, the functional status of gastric and pancreatic secretion during human acute pancreatitis is unknown. Thus, we compared the effects of nasogastric suction, intravenous glucagon (5 microgram/kg per hour), and cimetidine (2 mg/kg per hour) on the output of acid and pancreatic enzymes and the clinical course of human acute pancreatitis. In three subjects with acute alcoholic pancreatitis, gastric acid secretion was increased above normal and was decreased by glucagon and cimetidine used alone and in combination. In two of the three patients, duodenal output of trypsin and lipase was normal or increased and was reduced by glucagon and cimetidine given alone or in combination. Twenty patients with documented acute pancreatitis randomly received treatment with nasogastric suction, cimetidine alone, or the combination of cimetidine and glucagon. Four of the five complications observed during the trial occurred in the combination-treatment group (P less than 0.05). Administration of cimetidine alone or with glucagon did not improve the outcome when compared with nasogastric suction.