The first lesion of chronic calcifying pancreatitis (CCP), the most frequent form of chronic pancreatitis is the formation in the ducts of plugs build up of protein and calcium carbonate which are at the origin of pancreatic calculi. Pancreatic juice is supersaturated in calcium carbonate. A novel protein, the pancreatic stone protein (PSP) has been purified from human pancreatic juice and its amino-acid composition has been determined. It is biosynthesized in the acinar cell as well as enzymes. PSP prevents the formation of calcium carbonate crystals in a supersaturated solution. Its secretion is decreased in patients presenting with CCP. It is proposed that this decrease plays an important part in the pathogenesis of CCP.