As a continuation of work from this laboratory on anticholinesterase induced pancreatitis, a study of the relationship between reduced serum cholinesterase activity and changes in pancreatic intraductal pressure was undertaken. Pharmakokinetic studies in three dogs revealed rapid reduction in serum cholinesterase activity following an IV bolus dose of the cholinesterase inhibitor 0,0-diethyl-0-(2-isopropyl-6-methyl-4-pyrimidinyl)phosphorothioate. Following each dose of cholinesterase inhibitor, stable levels of cholinesterase inhibition were reached in 30 minutes. In four dogs the pancreatic duct was perfused from the tail of the ventral pancreas and intraductal pressures measured. A total of 25 mg/kg of the cholinesterase inhibitor was given in 5 mg/kg doses 30 minutes apart, and serum cholinesterase measured 30 minutes after each dose. Mean pressures were established over a 15 minute interval. Linear regression analysis of 23 data points revealed a significant (p < 0.001) cumulative dose-related increase in pancreatic intraductal pressure [Pressure (cm saline) = 14.2 + 1.03 x Cumulative Dose (mg/kg)] and significant (p< 0.001) negative correlation between serum cholinesterase activity and intraductal pressure [Pressure (cm saline) = 48.0 - 0.057 x Esterase Activity (mU/ml)]. These data suggest that, in dogs, reduced cholinesterase activity is directly related to increased pancreatic intraductal pressure, and it may be a factor in the pathogenesis of pancreatitis.