To investigate the role of lactoferrin in intraductal protein precipitates in chronic pancreatitis, lactoferrin was measured in pure pancreatic juice collected by endoscopic retrograde pancreatic cannulation using a sensitive and specific radioimmunoassay. Significant gradual increase in the lactoferrin concentration and output was observed in chronic pancreatitis (mean +/- SE = 1.13 +/- 0.04 microgram/ml, 1.61 +/- 0.44 microgram/min for five controls; 4.73 +/- 0.70 microgram/ml, 14.1 +/- 2.86 micrograms/min for 15 patients with noncalcified mild chronic pancreatitis; 23.6 +/- 4.7 micrograms/ml, 28.4 +/- 13.4 micrograms/min for four with chronic pancreatitis with visible protein plugs or calculi). The total protein in the juice gradually decreased in chronic pancreatitis (12.8 +/- 1.48 mg/ml for control, 7.6 +/- 1.37 for noncalcified, 5.2 +/- 1.27 for patients with plugs or calculi). Lactoferrin appears to rise as the disease progresses and although this may be important etiologically, it may also just be an accompanying protein which increases as the disease progresses.