Inhibition of intraduodenal trypsin stimulates pancreatic secretion in rats and swine. This finding is controversial in healthy humans. The present study was designed to find whether a 'negative-feedback' mechanism exists in man. A 7-lumen tube equipped with two balloons was passed into the duodenum in 18 healthy volunteers. During a constant intravenous infusion of secretin (0.1 CU/kg/h) the duodenum was perfused with 0.9% NaCl solution (20 ml/10 min). Polyethylene glycol (10 g/l) served as nonabsorbable marker. Aprotinin (0.5 X 10(6) KIU/10 min or 1 X 10(6) KIU/10 min) was perfused intraduodenally during periods of constant pancreatic enzyme secretion for 30 min. During perfusion of the trypsin inhibitor aprotinin an almost complete inhibition of trypsin could be observed. However, at the same time or following the perfusion of aprotinin a significant augmentation of amylase, lipase or volume secretion did not occur. Thus, in the present study a negative-feedback control of pancreatic exocrine secretion by the intraduodenal trypsin concentration in man could not be demonstrated.