The aim of this study was to define an optimum serum enzyme ratio for the diagnosis of chronic pancreatitis (CP) and for the evaluation of the stage of the disease. With this goal in mind, a simultaneous and interrelated analysis of different serum pancreatic enzymes was performed in 296 consecutive patients with clinically suspected CP. A total of 167 patients were finally diagnosed with CP and 129 with other digestive diseases (used as controls). Serum values of pancreatic amylase, lipase, immunoreactive trypsin, and their ratios were determined in every patient before final diagnosis was established. Stepwise logistic regression analysis was performed. As expected, abnormally low values of individual serum pancreatic enzymes in the diagnosis of CP were highly specific (92-98%) but very insensitive (20-32%). Their diagnostic usefulness was neither improved by calculation of their ratios nor by the use of multivariate logistic regression analysis. A low pancreatic amylase/lipase ratio correlated with advanced CP (p < 0.01), and had a high degree of accuracy (80.5%) in the evaluation of the stage of the disease (assessed by endoscopic retrograde pancreatography). In conclusion, while serum pancreatic enzymes have limited usefulness in the diagnosis of CP, the pancreatic amylase/lipase ratio could be a simple method for staging the disease.