Elastase 1 and immunoreactive trypsin were assessed by a RIA technique in the sera of 29 control subjects, 24 pancreatic cancer patients, 22 patients with chronic pancreatitis and 31 with extra-pancreatic diseases to ascertain and compare their usefulness in chronic pancreatic disease diagnosis. Increased levels of elastase 1 were detected in 60.9% of pancreatic cancer and in 61.1% of chronic pancreatitis patients; low values were found in only two subjects with pancreatic disease. A close correlation between the two enzymes was found in patients suffering from pancreatic cancer and chronic pancreatitis. These data suggest that serum elastase 1, as well as immunoreactive trypsin, is of limited value in chronic pancreatic disease diagnosis; increased levels of the two enzymes always occur simultaneously; low immunoreactive trypsin values together with normal elastase 1 serum levels are detectable in a number of patients with chronic pancreatitis and severe exocrine insufficiency.