Severe pancreatitis and a pseudocyst occurred in a patient following accidental ingestion of an anticholinesterase insecticide, a substance not previously known to produce pancreatitis. Experiments were done to elucidate the mechanism. In one group of dogs the pancreatic duct was perfused and intraductal pressures were measured. The cholinesterase inhibitor 0,0-diethyl-0-(2-isopropyl-6-methyl-4-pyrimidinyl)phosphorothioate (25 mg/kg) caused a significant increase in the mean intraductal pressure from 12 +/- 2.4 to 27.8 +/- 5.9 cm saline. In a second group of dogs pancreatic secretory rates were measured. Anticholinesterase (75 mg/kg) in combination with secretin infusion (1 U/kg/hr) caused a significant increase in the secretin stimulated flow rate from 0.13 to 0.56 cc/min. Atropine (75 microgram/kg) abolished the anticholinesterase induced pressure and secretory rate increases. In a third group of dogs administration of cholinesterase inhibitor 75 mg/kg and secretin infusion 2 U/kg/hr resulted in acute pancreatic interstitial edema, acinar cell vacuolization, hyperamylasemia and hyperlipasemia. These results suggest that occurrence of pancreatitis as a complication of anticholinesterase insecticide intoxication is the result of hypersecretion and pharmacologic ductal obstruction.