Lithostathine S2-5 inhibits in vitro crystal growth of CaCO3. We developed an antibody against the peptide region responsible for inhibitory effect to determine whether lithostathine S2-5 levels are different in the pancreatic juice of patients with and without chronic pancreatitis. The antibody against the synthetic peptide of the N-terminal end of lithostathine S2-5 detected lithostathine S2-5 but not lithostathine S1 or lithostathine extracted from pancreatic calculi. Lithostathine S2-5 was detected in samples of pancreatic juice protein by immunoblotting using the specific antibody. The concentration of lithostathine S2-5 was compared between control and chronic pancreatitis groups. The mean concentrations of lithostathine S2-5 were significantly (p = 0.002) lower in chronic pancreatitis, 16.3 mu g/mg of total protein, than in the control, 47.1 mu g/mg of total protein. A decreased concentration of lithostathine S2-5 seems to increase the risk of stone formation in the ducts during the course of chronic pancreatitis because of insufficient inhibition of CaCO3 crystal growth.