Plasma trypsin concentrations was measured using a specific radioimmunoassay in 50 normal subjects and in patients with 99 diabetes mellitus, 17 pancreatitis and 10 chronic liver disease. Decreased plasma trypsin levels were observed in diabetes mellitus and chronic pancreatitis, whereas significantly elevated plasma trypsin levels were observed in diabetic patients with nephropathy, and in patients with acute pancreatitis and chronic liver disease. In diabetic patients treated with diet and sulfonylurea plasma trypsin was 242±18ng/ml and 228±17ng/ml respectively which was not significantly different from the value of 270±18ng/ml in normal subjects. However, plasma trypsin in insulin-treated diabetic patients was 170±12ng/ml which was significantly lower than that in normal subjects. A negative correlation between plasma trypsin levels and either blood glucose levels or insulinogenic index, that is increment of plasma insulin from base line to 30 min value after 50g oral glucose tolerance test was observed in diabetic patients. Elevated plasma trypsin in patients with diabetic nephropathy and chronic liver disease may reflect the disorder of trypsin metabolism. High plasma trypsin level in acute pancreatitis is caused by uncontrolled leakage, and decreased plasma trypsin in chronic pancreatitis is due to the destruction of pancreatic tissue. These results suggest that the measurement of plasma trypsin is good parameter of not only exocrine pancreatic function but also endocrine pancreatic function.