Although serum amylase and lipase levels have been studied extensively in patients with renal disease, there are fewer data regarding trypsinogen levels in patients with end-stage renal disease (ESRD) treated with different dialytic modalities. We therefore evaluated the blood concentrations of trypsinogen, amylase, and lipase in asymptomatic patients with chronic renal insufficiency (CRI) and ESRD, to determine whether treatment modality or renal handling of these enzymes is important in determining steady-state levels in asymptomatic patients with chronic renal disease. Mean trypsinogen concentration levels were higher in hemodialysis (HD) patients and patients with CRI compared with normal subjects when values in the different groups were compared. There was no difference in the mean trypsinogen levels between patients treated with HD and those with CRI, between patients treated with chronic ambulatory peritoneal dialysis (CAPD) and those treated with HD, or between CAPD patients and patients with CRI. The mean circulating trypsinogen concentration was elevated more frequently and to a higher level than amylase or lipase in patients with CRI and ESRD. HD treatment did not result in a lowering of mean circulating pancreatic enzyme levels. We propose that decreased peripheral clearance, pancreatic overproduction, increased release from the pancreas, or a combination of these mechanisms is responsible, at least in part, for the increased plasma concentration of trypsinogen in patients with CRI, rather than simply a decrease in renal clearance.