The precise inhibitory action of gabexate mesilate (GM) on the various pancreatic enzymes remains unclear. We designed this study to investigate the enzyme inhibitory action of GM in the serum and directly in the pancreatic juice. We observed 16 cases with postoperative pancreatic drainage. Patients were randomly assigned to one of two groups, to receive GM at a dose of 600 mg/24 hr (treated group: 8 patients) or a physiological solution (control group: 8 patients) by continuous intravenous infusion. In both groups pancreatic juice and serum were sampled three times: before infusion began (T0) and at 12 hr (T1) and 24 hr after infusion ended (T2). At the end of the study, seven patients received octreotide and the volume of pancreatic secretion was determined. No statistical difference was observed in serum amylase and phospholipase A2 activity in the treated and control groups. On the contrary, amylase and phospholipase A2 activity in the pancreatic juice diminished significantly only in the treated group, and in these patients a GM metabolite was also detectable in the pancreatic secretion. The volume of pancreatic secretion decreased only after infusion of octreotide. The enzyme inhibition in the pancreatic gland itself and the central role of inhibition of phospholipase A2 in the enzyme cascade responsible for activating other proteases, confirm the therapeutic use of GM in acute pancreatitis. An association of GM and octreotide during acute pancreatitis should be useful because of their different mechanisms. The precise inhibitory action of gabexate mesilate (GM) on the various pancreatic enzymes remains unclear. We designed this study to investigate the enzyme inhibitory action of GM in the serum and directly in the pancreatic juice. were randomly assigned to one of two groups, to receive GM at a dose of 600 mg / 24 hr (treated group: 8 patients) or a physiological solution (control group: 8 patients) by continuous intravenous infusion. serum were sampled three times: before infusion began (T0) and at 12 hr (T1) and 24 hr after infusion ended (T2). At the end of the study, seven patients received octreotide and the volume of pancreatic secretion was determined. No Statistical difference was observed in serum amylase and phospholipase A2 activity in the treated and control groups. On the contrary, amylase and phospholipase A2 activity in the pancreatic juice diminished significantly only in the treated group, and in these patients a GM metabolite was also detectable in the pancreatic secretion. The volume of pancreatic secretion decreased only after infusion of octreotide. The enzyme inhibition in the pancreatic gland itself and the central role of inhibition of phospholipase A2 in the enzyme cascade responsible for activating other proteases, confirm the therapeutic use of GM in acute pancreatitis. An association of GM and octreotide during acute pancreatitis should be useful because of their different mechanisms.